This case report describes a 63-year-old woman with idiopathic hypertrophic cranial pachymeningitis (IHCP) who was successfully treated with weekly subcutaneous methotrexate. IHCP is a rare disorder characterized by diffuse thickening of the dura mater, mostly associated with inflammation. The patient's symptoms initially improved with steroids but later worsened. MRI showed thickening of the dura and brain abnormalities. Treatment with weekly subcutaneous methotrexate led to complete clinical and radiological remission within 6 months, with minimal side effects. This is the first reported case of using low-dose methotrexate to successfully treat IHCP.
DARA BioSciences, Inc (NASDAQ: DARA) is a pharmaceutical development company that acquires promising therapeutic candidates and develops them through proof of concept (pre-phase III) in humans for subsequent sale or out-licensing to larger pharmaceutical companies.
KRN5500* for the treatment of neuropathic pain in patients with cancer – successfully completed a phase II study. KRN5500 met its primary endpoints of reduction of pain and safety. It was statistically significantly better than placebo (p=0.03). The company plans to initiate a second phase II this year in conjunction with the National Cancer Institute focusing on the treatment and prevention of chemotherapy induced peripheral neuropathy (CIPN). The NCI will sponsor these studies with DARA only having to supply active drug and placebo.
Have you ever tried to sleep in a brightly lit room with tubes and wires attached to you and people periodically talking to you ! moving you ! and touching you !
Inguinodynia: Chronic pain after inguinal hernia surgery by Dr. Avisak Bhatta...abhishak bhattacharjee
This is the presentation on Inguinodynia where a complete definition has been formulated. It was presented in conference of Asia Pacific Hernia Society 2017 in Kaohsiung, Taiwan.
DARA BioSciences, Inc (NASDAQ: DARA) is a pharmaceutical development company that acquires promising therapeutic candidates and develops them through proof of concept (pre-phase III) in humans for subsequent sale or out-licensing to larger pharmaceutical companies.
KRN5500* for the treatment of neuropathic pain in patients with cancer – successfully completed a phase II study. KRN5500 met its primary endpoints of reduction of pain and safety. It was statistically significantly better than placebo (p=0.03). The company plans to initiate a second phase II this year in conjunction with the National Cancer Institute focusing on the treatment and prevention of chemotherapy induced peripheral neuropathy (CIPN). The NCI will sponsor these studies with DARA only having to supply active drug and placebo.
Have you ever tried to sleep in a brightly lit room with tubes and wires attached to you and people periodically talking to you ! moving you ! and touching you !
Inguinodynia: Chronic pain after inguinal hernia surgery by Dr. Avisak Bhatta...abhishak bhattacharjee
This is the presentation on Inguinodynia where a complete definition has been formulated. It was presented in conference of Asia Pacific Hernia Society 2017 in Kaohsiung, Taiwan.
The longer the delay between the appearance of the first symptoms of Hansen’s Disease and the start of treatment, the more likely it is for nerve damage to occur
Pain Physicians should consider nerve blocks when systemic analgesics are failing. (Adjuvant therapy)
Careful selection of patients
Benefits should outweigh the risks
Thorough knowledge of the limitations and side effects
Need for randomized controlled clinical trials.
Post-discharge issues beyond pain in out-patient surgeryscanFOAM
A presentation by Johan Ræder at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
CHRONIC PAIN AND DEPRESSION: Cause or Effect or Linked?Sudhir Kumar
Chronic pain and depression are both common conditions, and in many patients, they co-exist. This presentation looks at the link between chronic pain and depression. Various drugs that can be used to treat chronic pain/depression have been discussed, with a special emphasis on tricyclic antidepressants.
The longer the delay between the appearance of the first symptoms of Hansen’s Disease and the start of treatment, the more likely it is for nerve damage to occur
Pain Physicians should consider nerve blocks when systemic analgesics are failing. (Adjuvant therapy)
Careful selection of patients
Benefits should outweigh the risks
Thorough knowledge of the limitations and side effects
Need for randomized controlled clinical trials.
Post-discharge issues beyond pain in out-patient surgeryscanFOAM
A presentation by Johan Ræder at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
CHRONIC PAIN AND DEPRESSION: Cause or Effect or Linked?Sudhir Kumar
Chronic pain and depression are both common conditions, and in many patients, they co-exist. This presentation looks at the link between chronic pain and depression. Various drugs that can be used to treat chronic pain/depression have been discussed, with a special emphasis on tricyclic antidepressants.
We asked business leaders to give their thoughts on the number of potential disrupters on the horizon for UK businesses when George Osborne addresses the nation on 16 March.
More Budget commentary is available at grantthornton.co.uk/budget
Шавкова В., Волкова А., Хандута А. Проект для "КонсультантПлюс Илан"prasu1995
Проект для компании «КонсультантПлюс Илан» (Красноярск)
Авторы: Алина Хандута (ИнАрхДиз АлтГТУ), Алиса Волкова, Вероника Шавкова (Связи с общественностью АлтГУ)
Выполнен в рамках интенсивного практического курса «Мастерская рекламы-3», Барнаул, 2012
Still’s Disease and Recurrent Complex Regional Pain Syndrome Type-I: The Firs...Samantha Adcock
Clinical Study
Still’s Disease and Recurrent Complex Regional Pain Syndrome
Type-I: The First Description
C´esar Faillace and Joz´elio Freire de Carvalho
Maintenance Electroconvulsive Therapy Augmentation on Clozapine-Resistant Psy...Zahiruddin Othman
Case Report: Maintenance electroconvulsive therapy augmentation on clozapine-resistant psychosis with neurosyphilis is effective and safe but has never been reported in the literature to the authors' knowledge. It is hoped that this case report would contribute to the scarce literature on this augmentation strategy
A case report of posterior reversible encephalopathy syndrome in a patient di...bijnnjournal
Posterior reversible encephalopathy syndrome (PRES), a clinical radiological syndrome, is characterized by the
abrupt development of neurological symptoms such as headaches, convulsions, altered sensorium, and visual
problems. PRES has been linked to a number of risk factors or etiologies, including the use of immunosuppressants
or cytotoxins, hypertensive encephalopathy, eclampsia, preeclampsia, and underlying autoimmune diseases.
A 41-year-old female was admitted with acute necrotizing emphysematous pancreatitis complicated by posterior
reversible encephalopathy syndrome
Tuberous sclerosis dr. amit vatkar, pediatric neurologistDr Amit Vatkar
Tuberous Sclerosis is a genetically inherited neurocutaneous syndrome can affect families in an autosomal dominant.
in this presentaion i will try and give u a review to the case and its management.
it will help u get a n outllook to diagnose a case of tuberous sclerosis
i have shown some images of the lesions present in the case to get a photographic memory.
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...clinicsoncology
Encephalitis caused by Herpes Simplex Virus (HSV) and medulloblastoma are both fairly rare disorders with relatively poor prognoses. We experienced a case of HSV encephalitis (HSE) in which the patient presented 1 year after surgical resection and radiation therapy and 1 month after chemotherapy....
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...SarkarRenon
Encephalitis caused by Herpes Simplex Virus (HSV) and medulloblastoma are both fairly rare disorders with relatively poor prognoses. We experienced a case of HSV encephalitis (HSE) in which the patient presented 1 year after surgical resection and radiation therapy and 1 month after chemotherapy....
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...georgemarini
Encephalitis caused by Herpes Simplex Virus (HSV) and medulloblastoma are both fairly rare disorders with relatively poor prognoses. We experienced a case of HSV encephalitis (HSE) in which the patient presented 1 year after surgical resection and radiation therapy and 1 month after chemotherapy....
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...AnonIshanvi
Encephalitis caused by Herpes Simplex Virus (HSV) and medulloblastoma are both fairly rare disorders with relatively poor prognoses. We experienced a case of HSV encephalitis (HSE) in which the patient presented 1 year after surgical resection and radiation therapy and 1 month after chemotherapy....
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...pateldrona
Encephalitis caused by Herpes Simplex Virus (HSV) and medulloblastoma are both fairly rare disorders with relatively poor prognoses. We experienced a case of HSV encephalitis (HSE) in which the patient presented 1 year after surgical resection and radiation therapy and 1 month after chemotherapy..
Herpes Simplex Encephalitis in Medulloblastoma Patients: Case Report and Revi...komalicarol
Medulloblastoma is the most common malignant solid tumor
in childhood, with the highest frequency among other brain tumors accounting for 30% of pediatric brain tumors and 7% to 8%
of all brain tumors. According to the World Health Organization
(WHO), medulloblastoma is classified as a grade IV tumor and
defined as “a malignant, invasive embryonal tumor of the cerebellum with preferential manifestation in children, predominantly
neuronal differentiation and an inherent tendency to metastasize
via cerebrospinal (CSF) pathways
Lateral medullary syndrome (LMS) is a type of ischemic stroke
which occurs due to disruption of the blood flow in vertebral artery, or posterior inferior cerebellar artery. LMS can present with
various sign and symptoms, depending on the site of infarct at the
medullary area. Typical LMS often affects the pain and temperature sensation over the contralateral extremities and ipsilateral face
of the infarct area. We illustrate a case of LMS with predominant
bulbar symptoms which is sparse the sensation and our treatment
experience.
Mortalidad asociada al diagnóstico de síndrome de Guillain-Barré en adultos i...Erwin Chiquete, MD, PhD
Mortality associated with a diagnosis of Guillain-Barré syndrome in adults of Mexican health institutions
Introduction. Guillain-Barré syndrome (GBS) is a neurological emergency representing the main cause of flaccid paralysis
around the world, affecting all age groups. Little is known about the essential epidemiology of GBS in most Latin American
countries.
Aim. To determine the mortality associated with the diagnosis of GBS in hospital discharges during 2010 in hospitals of
the Ministry of Health, Mexico.
Patients and methods. We analyzed the database of hospital discharges of institutions pertaining to the Ministry of
Health. Study cases were identified by the code G61.0 of the International Classification of Diseases, 10th revision (ICD-10).
We excluded records of patients younger than 18 years and patients without complete demographic information.
Results. During the year 2010 there were 2,634,339 discharges from hospitals of the Ministry of Health. We identified a
total of 467 hospitalizations due to GBS in adults (median age: 41 years; 62.1% male) from 121 health institutions of the
32 Republic States. The highest frequency of GBS hospitalizations occurred during summer and fall. The median hospital
stay was 8 days. The hospital mortality rate was 10.5%. The probability of death was directly associated with age, without
a particular trend regarding gender, hospital care or state.
Conclusions. In 2010 GBS hospital mortality in this part of the Mexican health system was higher than that reported in
contemporary studies. A seasonal association was observed regarding the frequency of hospitalizations for GBS.
Key words. Climate. Epidemiology. Guillain-Barré syndrome. Mortality. Mexico.
Rogelio Domínguez-Moreno, Paulina Tolosa-Tort, Anais Patiño-Tamez, Alejandra Quintero-Bauman,
Deisy K. Collado-Frías, María G. Miranda-Rodríguez, Obet J. Canela-Calderón, Pablo Hurtado-Valadez,
Raúl de Gante-Castro, Karoll M. Ortiz-Guillén, Bruno Estañol-Vidal, Horacio Sentíes-Madrid,
Guillermo García-Ramos, Carlos Cantú-Brito, José Luis Ruiz-Sandoval, Erwin Chiquete
Seroepidemiology of Toxoplasma gondii infection in drivers involved in road t...Erwin Chiquete, MD, PhD
Background: The prevalence of toxoplasmosis in the general population of Guadalajara, Mexico, is around 32%.
Toxoplasmosis can cause ocular lesions and slowing of reaction reflexes. Latent toxoplasmosis has been related
with traffic accidents. We aimed to assess the prevalence of anti-Toxoplasma gondii antibodies and visual
impairments related with traffic accidents in drivers from the metropolitan Guadalajara.
Methods: We prospectively evaluated the prevalence of IgG and IgM anti-T. gondii antibodies in 159 individuals
involved in traffic accidents, and in 164 control drivers never involved in accidents. Cases of toxoplasmosis
reactivation or acute infection were detected by PCR in a subset of 71 drivers studied for the presence of T. gondii
DNA in blood samples. Ophthalmologic examinations were performed in drivers with IgG anti-T. gondii antibodies
in search of ocular toxoplasmosis.
Results: Fifty-four (34%) traffic accident drivers and 59 (36%) controls were positive to IgG anti-T. gondii antibodies
(p = 0.70). Among the 113 seropositive participants, mean anti-T. gondii IgG antibodies titers were higher in traffic
accident drivers than in controls (237.9 ± 308.5 IU/ml vs. 122.9 ± 112.7 IU/ml, respectively; p = 0.01 by Student’s t
test, p = 0.037 by Mann–Whitney U test). In multivariate analyses, anti-T. gondii IgG antibody titers were consistently
associated with an increased risk of traffic accidents, whereas age showed an inverse association. The presence of
IgM-anti-T. gondii antibodies was found in three (1.9%) subjects among traffic accident drives, and in two (1.2%)
controls. Three (4.2%) samples were positive for the presence of T. gondii DNA, all among seropositive individuals.
No signs of ocular toxoplasmosis were found in the entire cohort. Moreover, no other ocular conditions were found
to be associated with the risk of traffic accidents in a multivariate analysis.
Conclusions: Anti-T. gondii antibody titers are associated with the risk of traffic accidents. We could not determine
any association of ocular toxoplasmosis with traffic accidents. Our results warrant further analyses in order to clarify
the link between toxoplasmosis and traffic accidents.
Tiempo de llegada hospitalaria y pronóstico funcional después deun infarto ce...Erwin Chiquete, MD, PhD
Introducción: La información sobre el tiempo de llegada hospitalaria después de un infartocerebral (IC) se ha originado en países con unidades especializadas en ictus. Existe poca infor-mación en naciones emergentes. Nos propusimos identificar los factores que influyen en eltiempo de llegada hospitalaria a 1, 3 y 6 h y su relación con el pronóstico funcional después delictus.Métodos: Se analizó la información de pacientes con IC incluidos en el estudio Primer RegistroMexicano de Isquemia Cerebral (PREMIER) que tuvieran tiempo definido desde el inicio de lossíntomas hasta la llegada hospitalaria. El desenlace funcional se evaluó mediante la escalamodificada de Rankin a los 30 días, 3, 6 y 12 meses.Resultados: De 1.096 pacientes con IC, 61 (6%) llegaron en < 1 h, 250 (23%) en < 3 h y 464 (42%)en < 6 h. Favorecieron la llegada temprana en < 1 h: el antecedente familiar de cardiopatíaisquémica y ser migra˜noso; en < 3 h: edad 40-69 a˜nos, antecedente familiar de hipertensión,antecedente personal de dislipidemia y cardiopatía isquémica, así como la atención en hospitalprivado; en < 6 h: antecedente familiar de hipertensión, ser migra˜noso, ictus previo, cardiopatíaisquémica y atención en hospital privado. La llegada hospitalaria tardía se asoció a ictus lacunary alcoholismo. Solo el 2,4% recibió trombólisis. Independientemente de la trombólisis, la llegadaen < 3 h se asoció a menor mortalidad a los 3 y 6 meses, además de menos complicacionesintrahospitalarias.
Comportamiento del barorreflejo en pacientes con síncope vasovagal durante el...Erwin Chiquete, MD, PhD
Caroline Malamud-Kessler, Bruno Estañol-Vidal, Óscar Infante-Vázquez, Miguel Campos-Sánchez,
Erwin Chiquete
Introducción. El síncope mediado neuralmente, también conocido como síncope vasovagal, se define como la pérdida
súbita y transitoria del estado de alerta como consecuencia de un descenso brusco y profundo de la presión arterial.
Objetivo. Conocer las diferencias de los parámetros hemodinámicos que median el barorreflejo durante el ortostatismo
activo en pacientes con diagnóstico clínico de síncope vasovagal y sujetos sanos.
Sujetos y métodos. Estudio transversal, observacional y comparativo. Se incluyeron 20 pacientes con diagnóstico de síncope
neuralmente mediado y 30 controles, a los que se les practicó la prueba de ortostatismo activo y se les registró por
finometría la presión arterial sistólica (PAS) y la frecuencia cardíaca (intervalo entre latidos) de manera continua (latido a
latido) y no invasiva.
Resultados. Los pacientes con síncope presentaron una PAS basal con una media significativamente mayor que la de los
sanos. Las magnitudes medidas desde la PAS basal demostraron una diferencia significativa, que era de menor valor en el
grupo de los controles. No se demostraron diferencias entre grupos en la caída de la PAS desde el primer pico, recuperación
de la PAS desde la sima o en las latencias medidas en la frecuencia cardíaca.
Conclusiones. La PAS basal y la caída de la PAS medida desde la basal en posición supina fue mayor en los pacientes con
síncope mediado neuralmente que en los sujetos sanos. La magnitud de la elevación de la frecuencia cardíaca tuvo una
tendencia a ser mayor en el grupo de pacientes en comparación con el grupo control. Esto sugiere una hiperactividad
simpática en los pacientes con síncope
Delírium en adultos que reciben cuidados paliativos: revisión de laliteratura...Erwin Chiquete, MD, PhD
Delírium en adultos que reciben cuidados paliativos: revisión de laliteratura con un enfoque sistemáticoSofía Sánchez-Romána, Cristina Beltrán Zavalab, Argelia Lara Solaresby ErwinChiquetea,∗
El delírium en pacientes que reciben cuidados paliativos es frecuente y constituyeun importante reto de diagnóstico y tratamiento. Nuestro objetivo fue realizar en 2 fases unanálisis bibliométrico de la evidencia científica reciente (2007 a 2012) sobre diagnóstico y tra-tamiento del delírium en adultos en cuidados paliativos. En la fase 1 (estudios descriptivos yrevisiones narrativas) se identificaron 133 artículos relevantes: 73 trataron el tema del delíriumde forma secundaria y en 60 artículos como tema principal. Sin embargo, solo se identificaron4 estudios observacionales prospectivos en los que el delírium fue central. De 135 artículos iden-tificados en la fase 2 (ensayos clínicos o estudios descriptivos sobre tratamiento del delírium enpacientes paliativos), solo 3 fueron sobre prevención o tratamiento: 2 estudios retrospectivosy un ensayo clínico sobre prevención multicomponente en pacientes con cáncer. Gran parte dela literatura reciente corresponde a revisiones que hablan de estudios realizados hace másde una década en pacientes diferentes a los que reciben cuidados paliativos. En conclusión, laevidencia científica reciente sobre el delírium en cuidados paliativos es escasa y subóptima.Urgen estudios prospectivos que se enfoquen específicamente en esta población altamentevulnerable.
Central Adiposity and Mortality after First-Ever Acute Ischemic StrokeErwin Chiquete, MD, PhD
Erwin Chiquete a José L. Ruiz-Sandoval c Luis Murillo-Bonilla e
Carolina León-Jiménez g Bertha Ruiz-Madrigal d, f Erika Martínez-López d, f
Sonia Román d, f Arturo Panduro d, f Alma Ramos b Carlos Cantú-Brito
Background: The waist-to-height ratio (WHtR) may be a better
adiposity measure than the body mass index (BMI). We
evaluated the prognostic performance of WHtR in patients
with acute ischemic stroke (AIS). Methods: First, we compared
WHtR and BMI as adiposity measures in 712 healthy
adults by tetrapolar bioimpedance analysis. Thereafter,
baseline WHtR was analyzed as predictor of 12-month allcause
mortality in 821 Mexican mestizo adults with first-ever
AIS by a Cox proportional hazards model adjusted for baseline
predictors. Results: In healthy individuals, WHtR correlated
higher than BMI with total fat mass and showed a higher
accuracy in identifying a high percentage of body fat (p <
0.01). In AIS patients a U-shaped relationship was observed
between baseline WHtR and mortality (fatality rate 29.1%).
On multivariate analysis, baseline WHtR ≤ 0.300 or >0.800 independently
predicted 12-month all-cause mortality (h
José L. Ruiz-Sandoval, Guadalupe Ramírez-Guzmán,
Erwin Chiquete and Ángel Vargas-Sánchez
A 45-year-old garbage collector was referred to our department
with a history of tonic-clonic seizures and risky
sexual behavior (anilingus). A neurological examination was
normal. Contrast-enhanced cranial CT showed calcified lesions
and viable parasites compatible with a diagnosis of
massive non-encephalitic neurocysticercosis. Oral metallic
implants impeded performing brain MRI. Hepatitis and HIV
serologies were negative. The patient was discharged with
steroids and an anticonvulsant. Delayed cysticidal therapy
was planned; however, albendazole therapy was immediately
initiated in another hospital, which led to brain edema, uncontrolled
seizures, rostrocaudal deterioration and death.
Cestoda infections are rare in developed countries (1). In
contrast, neurocysticercosis is a leading cause of adult-onset
epilepsy in Latin America. Massive infections are classified
as encephalitic or non-encephalitic (2). In patients with the
encephalitic presentation, cysticidal drugs can cause extensive
parasite lysis and aggravate brain inflammation (2). In
patients with non-encephalitic massive neurocysticercosis,
cysticidal therapy is usually considered; (2) however, rapid
initiation of antiparasitic medications can launch an encephalitic
process.
Cost of care according to disease-modifying therapy in Mexicans with relapsin...Erwin Chiquete, MD, PhD
Miguel A. Macı´as-Islas • Isaac F. Soria-Cedillo • Merced Velazquez-Quintana •
Victor M. Rivera • Vero´nica I. Baca-Muro • Edith A. Lemus-Carmona • Erwin Chiquete
Limited data exist on the costs of care of
patients with multiple sclerosis (MS) in low- to middleincome
nations. The purpose of this study was to describe
the economic burden associated with care of Mexican
patients with relapsing-remitting MS in a representative
sample of the largest institution of the Mexican public
healthcare system. We analysed individual data of 492
patients (67 % women) with relapsing-remitting MS registered
from January 2009 to February 2011 at the Mexican
Social Security Institute. Direct costs were measured about
the use of diagnostic tests, disease-modifying therapies
(DMTs), symptoms control, medical consultations,
relapses, intensive care and rehabilitation. Four groups
were defined according to DMT alternatives: (1) interferon
beta (IFNb)-1a, 6 million units (MU); (2) IFNb-1a, 12MU;
(3) IFNb-1b, 8MU; and (4) glatiramer acetate. All patients
received DMTs for at least 1 year. The most frequently
used DMT was glatiramer acetate (45.5 %), followed by
IFNb-1a 12MU (22.6 %), IFNb-1b 8MU (20.7 %), and
IFNb-1a 6MU (11.2 %). The mean cost of a specialised
medical consultation was €74.90 (US $107.00). A single
relapse had a mean total cost of €2,505.97 (US $3,579.96).
No differences were found in annualised relapse rates and
costs of relapses according to DMT. However, a significant
difference was observed in total annual costs according to
treatment groups (glatiramer acetate being the most
expensive), mainly due to differences in unitary costs of
alternatives. From the public institutional perspective,
when equipotent DMTs are used in patients with comparable
characteristics, the costs of DMTs largely determine
the total expenses associated with care of patients with
relapsing-remitting MS in a middle-income country.
Blood pressure at hospital admission and outcome after primary intracerebral ...Erwin Chiquete, MD, PhD
Introduction: The importance of the admission blood pressure (BP) for intracerebral
hemorrhage (ICH) outcome is not completely clear. Our objective was to
analyze the clinical impact of BP at hospital arrival in patients with primary ICH.
Material and methods: We studied 316 patients (50% women, mean age:
64 years, 75% with hypertension history) with acute primary ICH. The first BP reading
at admission was evaluated for its association with neuroimaging findings
and outcome. A Cox proportional hazards model and Kaplan-Meier analyses
were constructed to evaluate factors associated with in-hospital mortality.
Results: Intraventricular irruption occurred in 52% of cases. A high frequency
of third ventricle extension was observed in patients with BP readings in the
upper quartiles of the distribution (systolic, diastolic, or mean arterial pressure).
Blood pressure readings did not correlate with hematoma volumes. In-hospital
case fatality rate was 46% (63% among those with ventricular irruption). Systolic
BP (SBP) > 190 mm Hg was independently associated with in-hospital mortality
in supratentorial (n = 285) ICH (hazard ratio: 1.19, 95% confidence interval:
1.02-1.38, for the highest vs. the lowest quartile) even after adjustment for
known strong predictors (age, ICH volume, Glasgow coma scale and ventricular
extension). Blood pressure was not significantly associated with ventricular
extension or outcome in patients with infratentorial ICH.
Conclusions: A high BP on admission is associated with an increased risk of
intraventricular extension and early mortality in patients with supratentorial
ICH. However, a significant proportion of patients with high BP readings without
ventricular irruption still have an increased risk of death.
Serum Uric Acid and Outcome after Acute Ischemic Stroke: PREMIER StudyErwin Chiquete, MD, PhD
Background: Current evidence shows that uric acid is a potent
antioxidant whose serum concentration increases rapidly
after acute ischemic stroke (AIS). Nevertheless, the relationship
between serum uric acid (SUA) levels and AIS
outcome remains debatable. We aimed to describe the
prognostic significance of SUA in AIS. Methods: We studied
463 patients (52% men, mean age 68 years, 13% with glomerular
filtration rate <60 />2) at 30 days, or with
any outcome measure at 3, 6 or 12 months poststroke. After
adjustment for age, gender, stroke type and severity (NIHSS
<9),><24 h. Conclusions: A low SUA
concentration is modestly associated with a very good
short-term outcome. Our findings support the hypothesis
that SUA is more a marker of the magnitude of the cerebral
infarction than an independent predictor of stroke outcome.
Hepatitis C virus infection and type 2 diabetes mellitus in Mexican patients. Erwin Chiquete, MD, PhD
34. Chiquete E, Ochoa-Guzmán A, García-Lamas L, Anaya-Gómez F, Gutiérrez-Manjarrez JI, Sánchez-Orozco LV, Godínez-Gutiérrez SA, Maldonado M, Román S, Panduro A. Hepatitis C virus infection and type 2 diabetes mellitus in Mexican patients. Rev Med Inst Mex Seguro Soc. 2012;50(5):481-6. [PMID: 23282259]
Atherothrombotic Disease, Traditional Risk Factors, and 4-Year Mortality in a...Erwin Chiquete, MD, PhD
Erwin Chiquete, MD, PhD
Background: Atherothrombosis is becoming the leading cause of chronic morbidity in developing countries. This
epidemiological transition will represent an unbearable socioeconomic burden in the near future. We investigated
factors associated with 4-year all-cause mortality in a Latin American population at high risk.
Hypothesis: Largely modifiable risk factors as well as polyvascular disease are the main predictors of 4-year all-cause and
cardiovascular mortality in this Latin American cohort.
Methods: We analyzed 1816 Latin American stable outpatients (62.3% men, mean age 67 years) with symptomatic
atherothrombosis (87.1%) or with multiple risk factors only (12.9%), in the Reduction of Atherothrombosis for Continued
Health registry.
Results: Of patients with symptomatic atherothrombosis, 57.3% had coronary artery disease, 32% cerebrovascular disease,
and 11.7% peripheral artery disease at baseline (9.1% polyvascular). The main risk factors were hypertension (76%),
hypercholesterolemia (60%), and smoking (52.3%) in patients with established atherothrombosis; and hypertension
(89.7%), diabetes (80.8%), and hypercholesterolemia (73.9%) in those with risk factors only. Four-year all-cause mortality
steeply increased with none (6.8%), 1 (9.2%), 2 (15.5%), and 3 (29.2%) symptomatic arterial disease locations. In patients
with only 1 location, cardiovascular mortality was significantly higher with peripheral artery disease (11.3%) than with
cerebrovascular disease (6%) or coronary artery disease (5.1%). Significant baseline predictors of 4-year all-cause mortality
were congestive heart failure (hazard ratio [HR]: 3.81), body mass index<20 (HR: 2.32), hypertension (HR: 1.84), polyvascular
disease (HR: 1.69), and age ≥65 years (HR: 1.47), whereas statin use (HR: 0.49) and body mass index ≥30 (HR: 0.58) were
associated with a reduced risk.
Conclusions: Hypertension was the main modifiable risk factor for atherothrombosis and all-cause mortality in this Latin
José L. Ruiz-Sandoval, Erwin Chiquete,
Lucía E. Álvarez-Palazuelos, Miguel
A. Andrade-Ramos & Luis R. Rodríguez-
Rubio
Osmotic demyelination syndrome (ODS) is the
damage over the central nervous system caused by several
electrolytes, metabolic and toxic disorders. We aimed to
describe cases of unusual forms of ODS. In a 9-year period,
25 consecutive patients with ODS (15 men; mean age
42 years) were registered in our referral institution, among
them, four (16 %) with atypical neuroimaging findings
were abstracted for this communication. None of them
presented cardiorespiratory arrest, head trauma, seizures,
neuromyelitis optica spectrum or contact with toxic
chemicals. Case 1 was a 33-year-old alcoholic man without
hypertension or electrolyte imbalance, who presented a
classic central pontine myelinolysis (CPM) and a hemorrhage
within the pons. Case 2 was a 34-year-old alcoholic
man with hypoglycemia and hyponatremia who presented
CPM and diffuse bihemispheric extrapontine myelinolysis
(EPM) after correction of serum sodium. Case 3 was a
52-year-old woman with mild hypokalemia and hyponatremia
(inadequately corrected), who presented a peduncular
and cerebellar EPM. Case 4 was a 67-year-old
woman who had a suicidal attempt with antidepressants
and carbamazepine without impaired consciousness, who
complicated with mild hyponatremia associated with a
classical CPM and a spinal cord EPM. Case 2 died and the
rest remained with variable neurological impairments at
last follow-up visit. With modern neuroimaging, the
so-called atypical forms of ODS may not be as rare as
previously thought; however, they could have a more
adverse outcome than the classical ODS.
Spontaneous intracerebral hemorrhage in Mexico: results from a Multicenter Na...Erwin Chiquete, MD, PhD
Introduction. Scarce information exists on intracerebral hemorrhage (ICH) in Latin America, and the existent is derived
from single-center registries with non-generalizable conclusions. The aim of this study is to describe the frequency, etiology,
management and outcome of ICH in Mexico.
Patients and methods. We studied consecutive patients with ICH pertaining to the National Multicenter Registry on Cerebrovascular
Disease (RENAMEVASC), conducted in 25 centers from 14 states of Mexico. The Intracerebral Hemorrhage Grading
Scale (ICH-GS) at admission was used to assess prognosis at 30 days follow-up.
Results. Of 2,000 patients with acute cerebrovascular disease registered in RENAMEVASC, 564 (28%) had primary ICH
(53% women; median age: 63 years; interquartile range: 50-75 years). Hypertension (70%), vascular malformations (7%)
and amyloid angiopathy (4%) were the main etiologies. In 10% of cases etiology could not be determined. Main ICH
locations were basal ganglia (50%), lobar (35%) and cerebellum (5%). Irruption into the ventricular system occurred in
43%. Median score of ICH-GS was 8 points: 49% had 5-7 points, 37% had 8-10 points and 15% had 11-13 points. The 30-day
case fatality rate was 30%, and 31% presented severe disability. The 30-day survival was 92% for patients with ICH-GS 5-7
points, whereas it decreased to 27% in patients with ICH-GS 11-13 points.
Conclusions. In Mexico, ICH represents about a third of the forms of acute cerebrovascular disease, and the majority of
patients present severe disability or death at 30 days of follow-up. Hypertension is the main cause; hence, control of this
important cardiovascular risk factor should reduce the health burden of ICH.
An Expandable Prosthesis with Dual Cage-and-Plate Function in a Single Device...Erwin Chiquete, MD, PhD
Juan J. Ramı´rez, Erwin Chiquete, Juan J. Ramı´rez, Jr., Ernesto Go´mez-Limo´n, and Juan M. Ramı´rez
An expandable vertebral body prosthesis with dual cage-and-plate function in a single
device (JR prosthesis) was designed to test the hypothesis that this modular system can
provide the biomechanical requirements for immediate and durable spine stabilization
after corpectomy. Cadaver assays were performed with a stainless steal device to test fixation
and adequacy to the human spine anatomy. Then, 14 patients with vertebral tumors
(eight metastatic) underwent corpectomy and vertebral body replacement with a titaniummade
JR prosthesis. All patients had neurological deficit, severe pain and spine instability
prior to surgery. Mean pain score before surgery on a visual analog scale decreased from
7.6e3.0 points after operation ( p 5 0.002). All patients achieved at least one grade of
improvement in the Frankel score ( p 5 0.003), excepting the three patients with Frankel
grade A before surgery. Two patients with renal cell carcinoma died during the following
4 days after surgery. The remaining patients attained a painless and stable spine immediately,
which was maintained for long periods (mean follow-up: 25.4 months). No significant
infections or implant failures were registered. A nonfatal case of inferior vena cava
surgical injury was observed (repaired during surgery without further complications). In
conclusion, the JR prosthesis stabilizes the spine immediately after surgery and for the
rest of the patients’ life. To our knowledge, this is the first report on the clinical experience
of any expandable vertebral body prosthesis with dual cage-and-plate function in
a single device.
Expression profile of BRCA1 and BRCA2 genes in premenopausal Mexican women wi...Erwin Chiquete, MD, PhD
Gloria Loredo-Pozos, Erwin Chiquete,
Antonio Oceguera-Villanueva, Arturo Panduro,
Fernando Siller-Lo´pez, Martha E. Ramos-Márquez
Low BRCA1 gene expression is associated with
increased invasiveness and influences the response of
breast carcinoma (BC) to chemotherapeutics. However,
expression of BRCA1 and BRCA2 genes has not been
completely characterized in premenopausal BC. We analyzed
the clinical and immunohistochemical correlates of
BRCA1 and BRCA2 expression in young BC women. We
studied 62 women (mean age 38.8 years) who developed
BC before the age of 45 years. BRCA1 and BRCA2 mRNA
expression was assessed by reverse transcriptase-polymerase
chain reaction (RT-PCR) and that of HER-2 and
p53 proteins by immunohistochemistry. Body mass index
(BMI) C27 (52%) and a declared family history of BC
(26%) were the main risk factors. Ductal infiltrative adenocarcinoma
was found in 86% of the cases (tumor size
[5 cm in 48%). Disease stages I–IV occurred in 2, 40, 55,
and 3%, respectively (73% implicating lymph nodes).
Women aged B35 years (24%) had more family history of
cervical cancer, stage III/IV disease, HER-2 positivity, and
lower BRCA1 expression than older women (P-.05).
BRCA1 and BRCA2 expression correlated in healthy, but
not in tumor tissues (TT). Neither BRCA1 nor BRCA2
expression was associated with tumor histology, differentiation,
nodal metastasis or p53 and HER-2 expression.
After multivariate analysis, only disease stage explained
BRCA1 mRNA levels in the lowest quartile. Premenopausal
BC has aggressive clinical and molecular
characteristics. Low BRCA1 mRNA expression is associated
mainly with younger ages and advanced clinical stage
of premenopausal BC. BRCA2 expression is not associated
with disease severity in young BC women.
En conclusión, la neurotoxicidad por exposición
crónica a PDCB es rara y ha sido poco descrita
en la bibliografía. Las propiedades lipofílicas de
este compuesto producen desmielinización central,
y dan lugar a leucoencefalopatía difusa,
supra e infratentorial. Las manifestaciones más
frecuentemente descritas son agudas, y son de
interés particular, en nuestro paciente, las manifestaciones
cognitivas de tipo demenciales en
un seguimiento a largo plazo. Las recomendaciones
domésticas deben dirigirse a evitar el
contacto por parte de los menores de edad con
este compuesto, así como a su eventual sustitución
por productos menos tóxicos.
Spontaneous intracerebral hemorrhage in Mexico: results from a Multicenter Na...Erwin Chiquete, MD, PhD
José L. Ruiz-Sandoval, Erwin Chiquete, Alejandra Gárate-Carrillo, Ana Ochoa-Guzmán, Antonio Arauz,
Carolina León-Jiménez, Karina Carrillo-Loza, Luis M. Murillo-Bonilla, Jorge Villarreal-Careaga,
Fernando Barinagarrementería, Carlos Cantú-Brito, and the RENAMEVASC investigators
Introduction. Scarce information exists on intracerebral hemorrhage (ICH) in Latin America, and the existent is derived
from single-center registries with non-generalizable conclusions. The aim of this study is to describe the frequency, etiology,
management and outcome of ICH in Mexico.
Patients and methods. We studied consecutive patients with ICH pertaining to the National Multicenter Registry on Cerebrovascular
Disease (RENAMEVASC), conducted in 25 centers from 14 states of Mexico. The Intracerebral Hemorrhage Grading
Scale (ICH-GS) at admission was used to assess prognosis at 30 days follow-up.
Results. Of 2,000 patients with acute cerebrovascular disease registered in RENAMEVASC, 564 (28%) had primary ICH
(53% women; median age: 63 years; interquartile range: 50-75 years). Hypertension (70%), vascular malformations (7%)
and amyloid angiopathy (4%) were the main etiologies. In 10% of cases etiology could not be determined. Main ICH
locations were basal ganglia (50%), lobar (35%) and cerebellum (5%). Irruption into the ventricular system occurred in
43%. Median score of ICH-GS was 8 points: 49% had 5-7 points, 37% had 8-10 points and 15% had 11-13 points. The 30-day
case fatality rate was 30%, and 31% presented severe disability. The 30-day survival was 92% for patients with ICH-GS 5-7
points, whereas it decreased to 27% in patients with ICH-GS 11-13 points.
Conclusions. In Mexico, ICH represents about a third of the forms of acute cerebrovascular disease, and the majority of
patients present severe disability or death at 30 days of follow-up. Hypertension is the main cause; hence, control of this important cardiovascular risk factor should reduce the health burden of ICH.
Hemorragia intracerebral espontánea en México: resultados del Registro Hospit...Erwin Chiquete, MD, PhD
José L. Ruiz-Sandoval, Erwin Chiquete, Alejandra Gárate-Carrillo, Ana Ochoa-Guzmán, Antonio Arauz,
Carolina León-Jiménez, Karina Carrillo-Loza, Luis M. Murillo-Bonilla, Jorge Villarreal-Careaga,
Fernando Barinagarrementería, Carlos Cantú-Brito, investigadores RENAMEVASC
Introducción. Existe poca información respecto a la hemorragia intracerebral (HIC) en América Latina, y la existente ha
sido derivada de registros hospitalarios de un solo centro con conclusiones no generalizables. El objetivo de este estudio
es describir la frecuencia, etiología, manejo y desenlace clínico de la HIC en México.
Pacientes y métodos. Se estudiaron pacientes consecutivos con HIC incluidos en el Registro Nacional Mexicano de Enfermedad
Vascular Cerebral (RENAMEVASC), conducido en 25 centros de 14 estados de la República Mexicana. Se usó la
Intracerebral Hemorrhage Grading Scale (ICH-GS) para estimar el pronóstico a 30 días.
Resultados. De 2.000 pacientes con ictus agudo en el RENAMEVASC, 564 (28%) presentaron HIC espontánea (53% mujeres;
edad media: 63 años; rango intercuartílico: 50-75 años). La hipertensión arterial (70%), las malformaciones vasculares
(7%) y la angiopatía amiloidea (4%) fueron las causas más frecuentes. No se determinó la etiología en el 10% de
los casos. Las localizaciones más frecuentes fueron ganglionar (50%), lobar (35%) y cerebelosa (5%). La irrupción hacia
el sistema ventricular ocurrió en el 43%. La mediana en la escala ICH-GS al ingreso hospitalario fue de 8 puntos: el 49%
presentó 5-7 puntos; el 37%, 8-10 puntos, y el 15%, 11-13 puntos. La tasa de mortalidad a 30 días fue del 30%, y el 31%
mostró discapacidad grave. La sobrevida a 30 días fue del 92% en pacientes con 5-7 puntos en la escala ICH-GS, mientras
que se redujo al 27% en aquellos con 11-13 puntos.
Conclusiones. En México, la HIC representa casi un tercio de las formas de enfermedad vascular cerebral aguda, y la mayoría de los pacientes que la padecen presentan discapacidad funcional grave o muerte a 30 días. La hipertensión es la principal causa, por lo que el control de este importante factor de riesgo debería reducir la carga sanitaria de la HIC.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
1. Acta Neurochir (Wien) (2006) 148: 1011–1014
DOI 10.1007/s00701-006-0775-8
Case Report
Idiopathic hypertrophic cranial pachymeningitis successfully
treated with weekly subcutaneous methotrexate
J. L. Ruiz-Sandoval1 , G. Bernard-Medina2 , E. J. Ramos-Gomez1 , S. Romero-Vargas1 ,
´
S. Gutierrez-Urena2 , S. Gonzalez-Cornejo1 , and E. Chiquete1
´ ˜ ´
1
Department of Neurology and Neurosurgery, Hospital Civil ‘‘Fray Antonio Alcalde’’,
´
Universidad de Guadalajara, Guadalajara Jalisco, Mexico
2 ´
Department of Rheumatology, Hospital Civil ‘‘Fray Antonio Alcalde’’, Universidad de Guadalajara, Guadalajara Jalisco, Mexico
Received November 24, 2005; accepted February 26, 2006; published online April 18, 2006
# Springer-Verlag 2006
Summary as well as radiotherapy and surgical removal of the
Idiopathic hypertrophic cranial pachymeningitis is a very infrequent affected tissue, with rather limited success [9, 10]. Here
disorder. Adequate management is still a matter of debate. We describe we report on a patient with idiopathic hypertrophic cra-
the use of low-dose pulse methotrexate in treating a 63-year-old woman nial pachymeningitis (IHCP) successfully treated with
with idiopathic hypertrophic cranial pachymeningitis. A weekly scheme
with subcutaneous methotrexate was tried. Clinical improvement oc-
weekly subcutaneous methotrexate. To the best of our
curred in one week. Total remission of the clinical and neuro-imaging knowledge, this is the first report on the use of subcuta-
abnormalities was evident 6 months later, with minimal side effects. The neous methotrexate in the treatment of IHCP.
patient is in complete remission after one year of follow-up without
treatment. Hence, low-dose weekly subcutaneous methotrexate may be
safe and effective in inducing complete and sustained remission of this
Case report
condition. The experience with subcutaneous methotrexate to treat this
entity has never been reported. A 63-year-old woman was referred to our hospital in November 2002
Keywords: Dura mater; headache; inflammation; methotrexate; for exacerbation of her neurological deficits and atypical CT and MRI
pachymeningitis. findings. Her complaints began 4 years before (in 1998) with episodic
headaches. In 1999 the headaches increased in severity and frequency,
being daily associated with dizziness, otalgia and tinnitus, as well as
hearing and visual impairment. She had two generalised tonic-clonic
seizures, but no anti-epileptic drugs were prescribed. In 2000 she was
Introduction admitted to another hospital with diplopia, ataxic gait and mental dis-
turbances. She was initiated on steroid therapy with an acceptable
Hypertrophic pachymeningitis is characterised by dif- response for a short time, but with remissions and exacerbations of
fuse thickening of the dura mater, mostly associated her clinical complaints in the following months. No history of trauma,
with inflammation [10]. It is subdivided into cranial, intrathecal drug administration or contrasted spinal studies was declared.
At presentation to our hospital, neurological examination revealed
spinal and craniospinal types, the latter being the less slow mental processing, bilateral papilloedema, multiple bilateral cranial
common [9]. The main clinical manifestations are head- nerve palsies (nerves affected: II, IV, V, VI, VII, VIII) and ataxic gait.
ache, cranial nerve palsies and ataxia [7, 9, 10]. Hyper- CT scans performed 2 years before arrival to our centre showed diffuse
thickening of the dura at the posterior and middle cranial fossa, as well
trophic pachymeningitis can be caused by a variety of
as the pontocerebellar cistern. In our hospital, a gadolinium-enhanced
diseases, including systemic auto-immune disorders, MRI showed an 8 to 10 mm thickening of the dura in the same locations
malignancies, tuberculosis, fungal and HTLV-1 infec- with oedematous changes in anteromedial temporal and temporo-
tions [1, 7–10, 13]. However, most cases are of unknown occipital gyri (Fig. 1). There was no evidence of active or inactive forms
of neurocysticercosis.
aetiology. Several therapeutic strategies have been used, Blood analyses of C-reactive protein, erythrocyte sedimentation rate,
including steroids and other immunosuppressive agents, rheumatoid factor, complement components C3 and C4, P=C-antineu-
2. 1012 J. L. Ruiz-Sandoval et al.
Fig. 1. Pretreatment axial, coronal and sagital views of a T1-weighted MRI after gadolinium enhancement. Diffuse thickening of the dura with
oedematous changes in both anteromedial temporal and temporo-occipital lobes is evident
Fig. 2. Axial, coronal and sagital views of a gadolinium-enhanced T1-weighted MRI performed 6 months after having initiated the weekly
subcutaneous methotrexate scheme. Important improvement of the dura and brain parenchyma, with respect to basal MRI is evident
trophilic cytoplasmatic antibodies (ANCA), antinuclear antibodies, subcutaneous methotrexate (in November 2003) within a 6-month
tumoral markers, thyroid and hepatic functions, anti-HIV-1 and anti- period as follows: 4 months with subcutaneous methotrexate 6.25 mg
HIV-2 antibodies, VDRL test and fluorescent treponemal antibody test; weekly, and 2 months with oral methotrexate 2.5 mg weekly (complete-
yielded all normal results. Chest and cranial X-ray films had also normal ly discontinued in May 2004). During the course of the treatment the
findings. Lumbar puncture revealed an opening pressure of 200 mm patient reported minimal side effects, limited to a subtle pain at the
H2O. Laboratory CFS analysis showed pleocytosis with 169=mm3 cells sites of injection. The patient completed 12 months of follow up after
(90% mononuclear), protein 74 mg=dL and a CSF=plasma glucose ratio discontinuation of methotrexate, completely asymptomatic (by May
of 0.5 (50%). Gram and Ziehl-Neelsen stains were negative for patho- 2005).
genic micro-organisms. PCR assay for detection of Mycobacterium
tuberculosis DNA was negative. Three CSF samples were also nega-
tive for malignancies in cytological examinations. A CSF enzyme- Discussion
linked immunosorbent assay (ELISA) was positive for cysticercosis, at
low titres. Hypertrophic pachymeningitis has been increasingly
The patient refused brain surgery and biopsy. Hence, based on the reported since the introduction of CT and MRI. The
experience in other entities of auto-immune origin, we decided to initiate
treatment trying with a low-dose scheme of weekly subcutaneous metho- spine and cranio-cervical junction are the zones of pre-
trexate at a dose of 12.5 mg. The patient showed improvement of her ponderance for this affection, followed by the skull base
neurological deficits as early as 1 week after the first dose of metho- and less frequently by cortical regions [12, 15]. Clinical
trexate. One week later the patient was discharged with a final diagnosis
of IHCP, given the lack of evidence of a particular causative factor. At
manifestations are related to the topography of the
the 6 months follow up, and still under methotrexate treatment, the lesions and rarely are cause-specific. Chronic headache
patient was in complete remission of her neurological disturbances and signs of cranial neuropathies are the main clinical
and a new gadolinium-enhanced MRI showed a very important improve-
presentations [7, 9, 10]. Headache is almost invariably
ment of the previous abnormalities (Fig. 2). Based on two normal CSF
analyses at 8 and 12 months of treatment, and since the clinical mani- present, but does not show any specific pattern, except
festations of the disease were in sustained remission, we decided to taper when there is an associated hydrocephalus [10, 12].
3. Subcutaneous methotrexate in idiopathic pachymeningitis 1013
Ophthalmoplegia and optic nerve dysfunction are prob- efficacy [10]. Immunosuppressive agents as azathio-
ably the most important cranial nerve affections [9, 10, prine, cyclophosphamide and cytarabine have been tried
12]. Eventually the clinical picture may be that of with limited success [2, 9]. Hidden tuberculosis as the
Tolosa-Hunt or Garcin syndrome [8]. Differential diag- elusive aetiology of IHCP has been suggested, and
nosis is wide. In immunocompromised patients, syphillis empirical treatment with antituberculous medications
and tuberculosis could be frequent. Neoplasms such has been used [14]. Radiation therapy has also been
as lymphoma, a variety of adenocarcinomas, melanoma given [11].
and meningeal carcinomatosis can also cause pachy- Methotrexate is an antifolate with immunosuppressive
meningitis [10]. Brain and meninges are affected in and anti-inflammatory properties, which inhibits the pro-
approximately 10% of patients with Wegener’s granulo- liferation of lymphocytes (notably the CD3 and CD4
matosis, being the presence of cANCA highly sugges- subtypes) [5, 6]. It also reduces pro-inflammatory Th-1
tive of this disease [8]. cytokines and enhances Th-2 cytokines with anti-inflam-
In our patient, an exhaustive clinical and serological matory properties [5, 6]. Methotrexate has been used as
approach was inconclusive regarding a rheumatological high-dose pulse therapy for treatment of malignancies
diagnosis. Indeed, the positive CSF ELISA test for neu- since 1947. On the other hand, low-dose pulse metho-
rocysticercosis needs comment. In this case no past or trexate (given weekly as 7.5 to 30 mg orally or subcuta-
present evidence on neuroimaging exists for active or neously) was introduced in the 1950s for the treatment
inactive forms of neurocysticercosis to be considered of patients with psoriasis and psoriatic arthritis [5]. This
[3]. Hence, this test result could be a false-positive, or low-dose weekly scheme has also been used to treat
could indicate a past exposure without current clinical other inflammatory conditions with encouraging results
significance [4]. Moreover, biological or methodological [6]. Low-dose methotrexate is given parenterally to
false-positive results can be yielded by CSF ELISA test ensure effective compliance and uniform availability,
for neurocysticercosis, as those observed in the context as compared with the oral route [5, 6]. Also, subcuta-
of CNS infections (e.g., syphilis), subarachnoid hae- neous methotrexate is better tolerated [5]. The rationale
morrhage, neoplasms, degenerative diseases and other of this low-dose scheme is quite simple. Methotrexate is
inflammatory processes [3]. stored as polyglutamates in the intracellular space of
MRI is the most useful method of evaluating a patient monocytes, erythrocytes and hepatocytes (among other
with suspected thickening of the meninges [10]. Periph- cells); this intracellular accumulation allows drug ad-
eral enhancement and T2 hyperintensity are common in ministration once weekly as a bolus or divided into three
the early stages, corresponding to inflammation, while equal subdoses [5]. Based on these assumptions, and
hypo-intensity is attributed to fibrosis. Biopsy of the given that IHCP may have a similar pathophysiological
thickened dura mater is useful for confirmation of the mechanism to other conditions in which low-dose meth-
inflammatory process and for orientation of the aetiolo- otrexate has been proven effective in inducing re-
gical diagnosis [10]. Since our patient refused any inva- missions, we decided to give the patient a trial with
sive procedure, we did not obtain a biopsy. Nonetheless, low-dose pulse methotrexate. In our experience with this
to our knowledge, the clinical course of this case, the case, this scheme is effective and well tolerated, and
results of laboratory examinations, as well as the basal may induce complete remission of the disease. Also,
and post-treatment MRI findings support the diagnosis the subcutaneous route could require less drug monitor-
of IHCP. Furthermore, it has been demonstrated that ing than the oral route, an issue that, however, deserves
histological findings closely correlate to those in the more study. Nevertheless, the uncommon frequency of
gadolinium-enhanced MRI, as much before as during IHCP precludes the design of large randomised con-
the treatment [10]. trolled trials aimed to prove the tolerability and efficacy
Medical treatment of IHCP remains, controversial. of methotrexate at different doses and routes of admin-
Very interesting and imaginative approaches have been istration. The best treatment could prove efficacy with
proposed. However, steroid therapy is the most widely time, unfortunately based mostly on reports of isolated
used pharmacological treatment; nevertheless, usually cases or small case series.
there is an inevitable progression of the disease and In conclusion, weekly subcutaneous methotrexate
many cases may eventually become steroid-dependent may be safe and effective in treating IHCP. However,
for relapse to be avoided [7]. Pulse therapy with methyl- as the first report on this issue, this communication
prednisolone has been advocated in order to increase should be considered only a hypothesis-generating work
4. 1014 J. L. Ruiz-Sandoval et al.: Subcutaneous methotrexate in idiopathic pachymeningitis
waiting for systematic confirmation, or for the test of hypertrophic pachymeningitis and multiple cranial neuropathies:
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Correspondence: Jose L. Ruiz-Sandoval, Servicio de Neurologıa ´
13. Nagashima T, Maguchi S, Terayama Y, Horimoto M, Nemoto M, ´
y Neurocirugıa, Hospital Civil de Guadalajara ‘‘Fray Antonio
Nunomura M, Mori M, Seki T, Matsukawa S, Itoh T, Nagashima K Alcalde’’, Hospital 278, Guadalajara, Jalisco 44280, Mexico. e-mail:
(2000) P-ANCA positive Wagener’s granulomatosis presenting with jorusan@mexis.com