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Atypical parkinsonism

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ATYPICAL PARKINSONISM- PARKINSON PLUS SYNDROMES- AN UPDATE

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Atypical parkinsonism

  1. 1. ATYPICAL PARKINSONISM DR.SARATH MENON.R, MD(Med.),DNB(Med.),MNAMS DM RESIDENT DEPT. OF NEUROSCIENCES AIMS,KOCHI
  2. 2. OUTLINE  Classifications  Red flag signs  AP- syndromic approach  Diagnostic criteria  Phenotypic spectrum  Atypical AP or mimickers  Investigations  Novel biomarkers  Treatment  Future trends
  3. 3. INTRODUCTION  Common problem in neurology outpatient departments  Wide variety of sporadic / heredodegenerative syndromes  Aetiologies vary widely  80-85% -IPD  Differentiation from other syndromes  Very important in prognostication and management
  4. 4. AKINETIC RIGID SYNDROMES - CLASSIFICATION  Primary (Idiopathic) Parkinsonism  Multisystem Degenerations  . Heredodegenerative Parkinsonism  Secondary (Acquired, symptomatic) Parkinsonism
  5. 5.  Primary Parkinsonism Parkinson’s Disease  - Sporadic Parkinson’s Disease  - Hereditary
  6. 6. MULTISYSTEM DEGENERATIONS (PARKINSONISM PLUS)  Progressive Supranuclear Palsy  Multiple System Atrophy (Shy-Dragger syn.) SND (MSA P) OPCA (MSA C)  Corticobasal Degeneration  Diffuse Lewy Body Disease  Lytico-Bodig disease (Parkinsonism Dementia ALS -Complex of Guam)  Progressive pallidal Atrophy  Parkinsonism dementia Complex  Pallido pyramidal Degenerations
  7. 7. HEREDO DEGENERATIVE  Hereditary Juvenile Dystonia Parkinsonism (AR Parkin Mutation)  Dopa - Responsive Dystonia  Huntington’s Disease  Wilson’s Disease  Hereditary Ceruloplasmin Deficiency  Frontotemporal dementia with parkinsonism  Mitochondrial Cytopathies with Striatal Necrosis  PKAN (Neurodegeneration associated with brain Iron accumulation; Hallervorden - Spatz Disease)
  8. 8.  Spinocerebellar Degenerations (Eg: MJD)  Gerstmann - Straussler - Scheinker Disease  Familial Progressive Subcortical Gliosis  Familial Basal Ganglia Calcification  Lubag(X Linked dystonia - Parkinsonism)  Ceroid Lipofuscinosis  Neuroacanthocytosis  Hereditary Haemochromatosis.  Neuroferritinopathy  Aceruloplasminemia
  9. 9. SECONDARY PARKINSONISM  Infectious Post- encephalitic  HIV; SSPE; Prion diseases  Drugs  Dopamine Receptor Blocking drugs, Reserpine, Tetrabenazine, Alpha Methyl Dopa, Lithium, Flunarizine, Cinnarizine.  Toxins  MPTP, Carbon monoxide, Manganese, Mercury, Carbon disulfide,Cyanide, Methanol.  Vascular -Multi infarct; Binswangers disease.  Trauma -Pugilistic Encephalopathy.  Parathyroid abnormalities;  Hypothyroidism;  Brain Tumors  Paraneoplastic  NPH  Psychogenic.
  10. 10. IDIOPATHIC PD  UK Brain Bank Criteria  bradykinesia and at least one of the following: rest tremor, rigidity, or postural instability.
  11. 11. RED FLAGS  Symmetric bradykinesia and rigidity  Absence of tremor  Prominent myoclonus  Limb apraxia  Alien limb phenomena  Impaired down gaze  Facial dystonia  Early loss of postural reflexes  L- dopa induced facial dyskinesias  Ataxia  Stridor  Early dysphagia  Spasticity  Early dementia or hallucinations  Early and prominent dysautonomia
  12. 12. MAJOR SYNDROMES  PSP  MSA  CBGD  DLBD
  13. 13. PATHOPHYSIOLOGY  Accurate diagnosis is necessary to understand pathogenesis  Two proteins mainly  Alpha synuclein - Pre synaptic protein - Aggregates in cell body & neurons – lewy body & lewy neuritis- PD & DLBD - glial cytoplasmic inclusion in MSA
  14. 14. TAUPATHY  4 repeat tau accumalates  NFT & in glia  Psp- astrocytic tufts  CBD- astrocytic plaques
  15. 15. PROGRESSIVE SUPRANUCLEAR PALSY  Steele et al—1964  5% of parkinsonian pts  Prevalence—4.9 / 100,000  Incidence 1.7 (50-59yrs) to 14.7(80-89yrs)  Commonly misdiagnosed as PD  Insidious onset  No pathologic proven cases have begun before the age of 40.
  16. 16.  Tauopathy-4-repeat t, 4R tauopathy).  always sporadic, few familial cases- - MAPT (microtubuli associated protein t) gene mtn.  Mitochondrial dysfunction & oxidative stress - pathophysiology of PSP
  17. 17. Postural Instability & EP Features :  Falls—backward  Poor postural reflexes  Rigidity –axial  Dysarthria—spastic,  Hypophonic  ataxic  Frontal release signs  Pseudobulbar palsy  L-DOPA UNRESPONSIVENESS
  18. 18.  Reduced blink rate and closure of eyelids due to eyelid dystonia or levator inhibition ( apraxia of eyelid opening)  square wave-jerks  on doll’s eye maneuver, there is improved range, as vestibulo-ocular reflex is preserved  Subcortical-type dementia  Typical facies- “surprised look”
  19. 19. NINDS–SPSP DIAGNOSTIC CRITERIA FOR PSP  Possible PSP Mandatory inclusion criteria:  gradually progressive disorder  onset age 40 or later  Either vertical supranuclear palsy or both slowing of vertical saccades  postural instability with falls within a year of disease onset  no evidence of other diseases that could explain the foregoing features, as indicated by exclusion criteria
  20. 20. Mandatory exclusion criteria:  recent history of encephalitis  alien limb syndrome  cortical sensory deficits  focal frontal or temporoparietal atrophy  hallucinations or delusions unrelated to dopaminergic therapy  cortical dementia of Alzheimer type  prominent, early cerebellar symptoms  unexplained dysautonomia
  21. 21. Supportive features:  symmetrical akinesia or rigidity  proximal more than distal  abnormal neck posture  especially retrocollis  poor or absent response of parkinsonism to levodopa  early dysphagia and dysarthria  early onset of cognitive impairment including two or more of: apathy, impairment in abstract thought, decreased verbal fluency, utilisation or imitation behaviour, or frontal release signs
  22. 22. Probable PSP Mandatory inclusion criteria  gradually progressive disorder  onset age 40 or later  vertical supranuclear palsy  prominent postural instability with falls within a year of disease onset  no evidence of other diseases that could explain the foregoing features, as indicated by exclusion criteria
  23. 23. Definite PSP Mandatory inclusion criteria:  clinically probable or possible PSP and histopathological evidence of typical PSP
  24. 24. PHENOTYPIC SPECTRUM OF PROGRESSIVE SUPRANUCLEAR PALSY  typical PSP phenotype- Richardson syndrome  PSP-p = PD at least at the initial stages, with asymmetric parkinsonism, rest-tremor, better levodopa response, longer mean survival  pure akinesia with gait freezing (PSP-PAGF)  corticobasal syndrome (PSP-CBS),  frontotemporal dementia (PSP-FTD), progressive nonfluent aphasia  no clinical sign to predict PSP pathologic abnormality accurately in the non-RS phenotypes
  25. 25. INVESTIGATIONS  clinical diagnosis  MRI- midbrain atrophy Superior cerebellar peduncle atrophy. “morning glory flower sign” and the “hummingbird sign” are quite specific but show low sensitivity (50% and 68.4%, respectively  (DATscan) is abnormal in PD and all AP syndromes
  26. 26.  differentiate with PD, [123]meta-iodobenzylguanidine (MIBG) and 123I-iodobenzamide (IBZM) SPECT may be useful  MIBG is abnormal in PD because of postganglionic sympathetic denervation, but is typically normal in PSP.  IBZM SPECT assessing the postsynaptic receptors is abnormal in PSP and normal in PD  IBZM SPECT is abnormal in all APs and therefore cannot differentiate between PSP and other AP  Novel diagnostic approaches and biomarkers - csf tau protein -neurofilament light chain
  27. 27. PATHOLOGY  Neurofibrillary tangles are present in these areas.  Tufted astrocytes (Gallyas-positive) -hallmark feature of PSP that differentiates other 4R tauopathies such as CBD (astrocytic plaques
  28. 28. RX  no effective symptomatic or neuroprotective treatments  A trial of levodopa (up to 1 g/d) and amantadine (up to 450 mg/d)  Botulinum toxin injections can be used to treat levator inhibition.  Serotonin reuptake inhibitors (SSRIs) may be used for apathy with no clear benefit.  A small study with Coenzyme Q10- no RCT study  Recent large, double-blind studies with GSK-3b inhibitors (Tideglusib, Davunetide) have failed to show any clinical effect.  Tideglusib reduced the rate of brain atrophy in one study.  Supportive measures such as physiotherapy, walking aids, speech therapy and PEG
  29. 29. MULTIPLE SYSTEM ATROPHY :  Sporadic neurodegenerative disorder clinically any combination of parkinsonian, autonomic, cerebellar, or pyramidal signs  Pathologically– cell loss, gliosis, and glial cytoplasmic inclusions in several CNS structures.  MSA is an a-synucleinopathy  usually a sporadic disease; however, rarely, familial cases - mutations in COQ2 gene
  30. 30.  Epidemiology :  prevalence of MSA in four studies ranged from 1·9 to 4·9 cases per 100 000 people.  similar to those of other well-known neurodegenerative disorders such as Huntington’s disease and motor neuron disease.  no single environmental factor shown to increase or to reduce risks of MSA
  31. 31. Clinical presentation :  affects both men and women  the sixth decade of life progresses with a mean survival of 6–9 years.  substantial variation of disease progression with survival of more than 15 yrs. main features –  autonomic failure  Parkinsonism  cerebellar ataxia  pyramidal signs in any combination.
  32. 32. TWO MAJOR MOTOR PRESENTATIONS  distinguished clinically–  Parkinsonian features predominate in 80% of patients (MSA-P subtype),  cerebellar ataxia is the main motor feature in 20% of patients (MSA-C subtype).  Both similar survival times.  patients with MSA-P have a more rapid functional deterioration than those with MSA-C
  33. 33.  MSA-P-associated parkinsonism :  progressive akinesia and rigidity  jerky postural tremor and tremor at rest.  orofacial or craniocervical dystonia associated with a characteristic quivering high-pitched dysarthria.  Postural stability is compromised early on in the disease course  recurrent falls at disease onset are unusual in contrast to psp.
  34. 34.  90% of the MSA-P pts- unresponsive to levodopa in the long term.  50% have levodopa-induced dyskinesia affecting orofacial and neck muscles, without motor benefit.  fully developed clinical picture of MSA-P evolves within 5 years of disease onset, allowing a clinical diagnosis during follow-up.
  35. 35. MSA –P RED FLAGS  Early instability  Rapid progression  Pisa syndrome,camptocormia,contractures  Bulbar dysfunction  Respiratory dysfn- stridor,insp sighs  Emotional incontinence  2/6 – probable MSA-P – additional criteria
  36. 36. MSA-C :  gait ataxia  limb kinetic ataxia  scanning dysarthria,  cerebellar oculomotor disturbances.  Most patients develop additional non-cerebellar symptoms and signs  may be indistinguishable from other patients with idiopathic late onset cerebellar ataxia
  37. 37.  Dysautonomia :  urogenital and orthostatic dysfunction.  Early erectile dysfunction is nearly universal in men with MSA  Female- genital insensitivity  urinary incontinence or retention are common early in the course or as presenting symptoms
  38. 38. CONSENSUS STATEMENT FOR THE CLINICAL DIAGNOSIS OF MSA  clinical domains,  features  criteria used in the diagnosis of MSA
  39. 39.  Autonomic and urinary dysfunction :  Features  1. Orthostatic hypotension  2. Urinary incontinence or incomplete bladder emptying Criteria  Reduction of least 30mmHg or in diastolic blood pressure by at least 15 mm Hg after 3 min of standing  urinary incontinence (persistent, involuntary partial or total bladder emptying, accompanied by erectile dysfunction in men) or both
  40. 40.  Parkinsonism :  A. Features  1. Bradykinesia  2. Rigidity  3. Postural instability (not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction) 4. Tremor (postural, resting or both)  B. Criteria  Bradykinesia plus at least one of features 2–4
  41. 41.  Cerebellar dysfunction :  A. Features  1. Gait ataxia  2. Ataxic dysarthria  3. Limb ataxia  4. Sustained gaze-evoked nystagmus  Criteria  Gait ataxia plus at least one of features 2–4
  42. 42.  Corticospinal tract dysfunction  A. Features  1. Extensor plantar responses with hyper-reflexia  Criteria  Corticospinal tract dysfunction in MSA: no corticospinal tract features are used in defining the diagnosis of MSA  prominent and severe spasticity should raise suspicion for an alternative diagnosis
  43. 43. Consensus statement: exclusion criteria for the diagnosis of MSA :  History  Symptomatic onset under 30 years of age  Family history of a similar disorder  Systemic disease or other identifiable causes  Hallucinations unrelated to medication  DSM IV criteria for dementia  Prominent slowing of vertical saccades or vertical supranuclear gaze palsy  Evidence of focal cortical dysfunction such as aphasia, alien limb syndrome, and parietal dysfunction  Laboratory investigation- Metabolic, molecular genetic and imaging evidence of an alternative cause of features
  44. 44. DIAGNOSTIC CLINICAL APPROACH Motor signs  Parkinsonism poorly responsive to levodopa  Cerebellar ataxia  Pyramidal signs  Early instability and falls Within 3 years of disease onset  Rapid progression (wheelchair sign) despite dopaminergic treatment within 5 years of disease onset
  45. 45.  Orofacial dystonia or dyskinesias  Atypical spontaneous or levodopa induced dystonia  dyskinesia mainly affecting orofacial muscles, [resembling risus sardonicus of cephalic tetanus]  Axial dystonia -Pisa syndrome (subacute axial dystonia with a severe tonic lateral flexion of the trunk, head, and neck)  early severe camptocormia  Disproportionate antecollis -Chin on chest, neck can only be passively and forcibly extended to its normal position with difficulty; despite severe chronic neck flexion, flexion elsewhere is minor.
  46. 46.  Jerky tremor  Irregular myoclonic postural or action tremor of the hands or fingers  Dysarthria- - Atypical quivering, irregular and severely hypophonic or slurring high pitched dysarthria, - tends to develop earlier and be more severe than in PD  notable dysphagia
  47. 47. Non-motor signs  Severe dysautonomia  Abnormal respiration  Nocturnal (harsh or strained, high pitched inspiratory sounds) or diurnal inspiratory stridor,  involuntary deep inspiratory sighs and gasps, sleep apnoea  snoring increased from premorbid level  newly arisen REM sleep behaviour disorder  Emotional incontinence
  48. 48. “RED FLAGS’’  RBD and autonomic failure- pre motor stage  Early falls and postural instability can be seen- look for eye signs & fronto-subcortical dysfunction for PSP  L-dopa induced oro facial dystonia- MSA  Raynaud phenomenon is a common in MSA  Freezing of gait may be prominent, early, and severe, causing diagnostic difficulties -PSP -PAGF phenotype  dementia, it is considered a non supporting feature for the diagnosis of MSA  frank, prominent, early dementia should lead the clinician to other diagnoses.
  49. 49. Investigations  Autonomic function tests  Cardiovascular function test-within in 2-3 ys  Bladder function tests  standard urine analysis will exclude infection.  The residual volume –usg,cystometry ,UDS
  50. 50. IMAGING  MRI - Hot cross burn sign- mcp/pons- MSA-c - Putaminal rim- MSA-p - DAT scan - abnormal in all MSA, PSP, and PD - MIBG scintigraphy - abnormal in PD, normal in MSA  IBZM SPECT is normal in PD,abnormal in MSA (but also in PSP and CBD)
  51. 51. NOVEL BIOMARKERS  Mollenhauer and colleagues- CSF mean a-synuclein levels , not total t, or Ab42 levels differentiated PD and MSA from neurologic controls (70% sensitivity, 53% specificity)  a-synuclein and phosphorylated t/total t could differentiate PD from MSA -sensitivity of 90% & specificity of 71%  Flt3 ligand, a cytokine PD and MSA with a sensitivity of 99% and a specificity of 95%.
  52. 52. RX  Symptomatic  PD- L-dopa/ dopa agonists- cranio cervical dystonia postural hypotension Amantidine- gait disturbances  Orthostatic hypotension- high salt, fludrocortisone,midodrine  Urinary dysfunction - UDS- characterise nature -Neurogenic bladder- Oxybutinin or Tolderotidne  Erectile dysfunction- - sildenafil -intracavernosal inj. Or penile implants
  53. 53.  Emotional incontinence - SSRI/TCA RCT – Rasagiline and rifampicin- no effects Promising studies - IVIG - Intrarterial/IV autologous stem cells - Future - Alpha synuclein targeting antibodies
  54. 54. CORTICOBASAL DEGENERATION : sixth to eighth decades of life, onset of symptoms at mean age 63 years (SD 7·7) . sporadic disease 4–6% of parkinsonism,
  55. 55. Clinical presentations  Five initial presentations  The most common presentation (55%) -“useless arm” (ie, a rigid, dystonic, akinetic, or apraxic arm),  gait disorder (27%)  prominent sensory symptoms  isolated speech disturbance  behavioural disturbance
  56. 56.  Clinical features Motor Limb clumsiness (asymmetric) Bradykinesia/Akinesia (asymmetric) Rigidity (asymmetric) Tremor (action/postural) Myoclonus Limb dystonia (asymmetric) Blepharospasm Choreoathetoid movements Speech abnormalities Gait disorder
  57. 57. Higher cortical functions  Apraxia (limb more common than orofacial, eyelid- opening)  Dementia  Alien-limb phenomenon  Aphasia  Frontal-lobe-release signs  Cortical sensory abnormalities  Depression  apathy  Anxiety Irritability  Disinhibition  Delusions  Obsessive compulsive disorder
  58. 58. DIAGNOSTIC CRITERIA FOR CORTICOBASAL DEGENERATION Inclusion criteria (one of A or B) A) Rigidity (easily detectable without reinforcement) and one cortical sign:  apraxia (more than simple use of limb as object; absence of cognitive or motor deficit sufficient to explain disturbance)  cortical sensory loss (preserved primary sensation, asymmetric)  alien-limb phenomenon (more than simple levitation) B) Asymmetric rigidity, dystonia (focal in limb; present at rest at onset),  focal reflex myoclonus (spreads beyond stimulated digits
  59. 59. Exclusion criteria  Early dementia (will exclude some patients with corticobasal degeneration)  Early vertical gaze palsy  Rest tremor  Severe autonomic disturbances  Sustained responsiveness to levodopa  Lesions on imaging studies indicate another pathological process
  60. 60. PROPOSED CRITERIA FOR THE DIAGNOSIS OF CORTICOBASAL DEGENERATION Core features  Insidious onset and progressive course  No identifiable cause (eg, tumour, infarct)  EPS – one of the follow -focal or asymmetric appendicular rigidity -lacking prominent and sustained l-dopa response -focal or asymmetric appendicular dystonia  Cortical dysfunction - at least one of the following : focal or asymmetric ideomotor apraxia alien-limb phenomena cortical sensory loss visual or sensory hemineglect constructional apraxia focal or asymmetric myoclonus apraxia of speech or nonfluent aphasia
  61. 61. Supportive investigations  Variable degrees of focal or lateralised cognitive dysfunction,  with relative preservation of learning and memory on neuropsychometric testing  Focal or asymmetric atrophy on CT or MRI imaging, typically in perifrontal cortex  Focal or asymmetric hypoperfusion on SPECT or PET, typically maximal in parietofrontal cortex with or without basal ganglia involvement
  62. 62. NEUROPATHOLOGICAL CRITERIA Core features  Focal cortical neuronal loss  Substantia nigra neuronal loss  Cortical and striatal Gallyas/tau-positive neuronal and glial lesions, especially astrocytic plaques and threads, in both white and grey matter Supportive features  Cortical atrophy, commonly with superficial spongiosis  Ballooned neurons, in atrophic cortices  Tau-positive oligodendroglial coiled bodies
  63. 63. PHENOTYPIC SPECTRUM OF CORTICOBASAL DEGENERATION  Classic CBD phenotype- CBS  CBD- present with FTD,RS,PPA,PCA  AD,PSP,FTD present with CBS  Symmetrical bilateral CBS- AD pathology/RS  Early onset PSP – CBD pathology  For which proposed clinical criteria applied
  64. 64. INVESTIGATIONS  Imaging asymmetric frontal, and parietal cortical atrophy becomes evident with dilatation of the lateral ventricle  EEG – -normal at first - show asymmetric slowing that is maximum over the hemisphere contralateral to the more affected limb  Dopamine transporter SPECT- abnormal - differentiate them from those with Alzheimer’s and Pick’s diseases (in whom this scan is typically normal) early in the course of the disease.
  65. 65.  FDG-PET - Asymmetric reduction in fronto parietal regions
  66. 66. RX  Anecdotal  L-dopa trial (upto 1 gm/d)/Amantadine- PD symptoms  Valproate, Levetiracetam- myoclonus  Botox inj- dystonic hand  No trials with ACEI – dementia  Palliative rx
  67. 67. “CORTICO BASAL DEGENERATION-LOOKALIKE” SYNDROMES  atypical manifestations of PSP  -progressive nonfluent aphasia FTD.  Parkinson’s disease  multiple-system atrophy  Wilson’s disease  progressive subcortical gliosis  rigid-akinetic type Huntington’s disease  atypical Pick’s disease  parkinsonism– dementia–amyotrophic-lateral-sclerosis complex  prion related disease  sudanophilic leukodystrophy  neurofilament inclusion disease.
  68. 68. DEMENTIA WITH LEWY BODIES Central feature (essential for a diagnosis of possible or probable DLB)  Dementia -progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function.  Prominent or persistent memory impairmen- not occur in the early stages ,usually evident with progression.  Deficits on tests of attention, executive function, and visuospatial ability may be especially prominent.
  69. 69. CORE FEATURES (TWO CORE FEATURES ARE SUFFICIENT FOR A DIAGNOSIS OF PROBABLE DLB, ONE FOR POSSIBLE DLB)  Fluctuating cognition with pronounced variations in attention and alertness  Recurrent visual hallucinations that are typically well formed and detailed  Spontaneous features of parkinsonism
  70. 70. SUGGESTIVE FEATURES  REM sleep behavior disorder  Severe neuroleptic sensitivity  Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging  (If one or more of these is present in the presence of one or more core features, - probable DLB .  In the absence of any core features, one or more suggestive features is sufficient for possible DLB.  Probable DLB should not be diagnosed on the basis of suggestive features alone.)
  71. 71. SUPPORTIVE FEATURES (COMMONLY PRESENT BUT NOT PROVEN TO HAVE DIAGNOSTIC SPECIFICITY)  Repeated falls and syncope  Transient, unexplained loss of consciousness  Severe autonomic dysfunction, e.g., orthostatic hypotension, urinary incontinence  Hallucinations in other modalities  Systematized delusions  Depression  Relative preservation of medial temporal lobe structures on CT/MRI scan  Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity  Abnormal (low uptake) MIBG myocardial scintigraphy  Prominent slow wave activity on EEG with temporal lobe transient sharp waves
  72. 72. A DIAGNOSIS OF DLB IS LESS LIKELY  If -CVA evident as focal neurologic signs or on brain imaging  In the presence of any other physical illness or brain disorder sufficient to account in part or in total for the clinical picture  If parkinsonism only appears for the first time at a stage of severe dementia
  73. 73. TEMPORAL SEQUENCE OF SYMPTOMS  diagnosed when dementia occurs before or concurrently with parkinsonism (if it is present).  Parkinson disease dementia (PDD) - dementia that occurs in the context of well-established Parkinson disease.  In research studies in which distinction needs to be made between DLB and PDD, the existing 1-year rule between the onset of dementia and parkinsonism - DLB continues to be recommended.
  74. 74. CLINICAL MANAGEMENT  Motor parkinsonism- -Levodopa at low doses & titrate up. -Anticholinergics should be avoided.  Neuropsychiatric symptoms.--cholinesterase inhibitors (CHEIs) or atypical antipsychotic
  75. 75. “ATYPICAL” ATYPICAL PARKINSONISM  Misdiagnosis PD with AP , as well as FTD,AD,PPA  Mimickers of Atypical PD Eg: SCAS/ FTAX- mimic MSA Neimann Pick C,CTX,prion d/s,mitochondrial- mimic AP phenotype - Age of onset - Tempo of progression - Family history - Clinical exam + associated features
  76. 76. SUMMARY  Careful clinical examination  Expanding phenotypic spectrum of AP & expanding pathological spectrum of classic AP phenotypes – diagnostic challenge  AP mimickers  Investigations may be supportive, but their sensitivity and specificity are low.  There are currently no biomarkers available.  There are currently no neuroprotective treatments available.  symptomatic and supportive treatments with usually no sustained effect.  Further research required
  77. 77. THANK YOU

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