Derived from Greek word “enkephalos”- meaning brain. “Pathos” meaning is disease. The term “encephalopathy” is defined as altered mental status as a result of a diffuse disturbance of brain function.

1. ENCEPHALOPATHY: TYPES, SYMPTOMS,
CAUSES, STAGES & TREATMENT
 Derived from Greek word “enkephalos”- meaning brain.
 “Pathos” meaning is disease.
 The term “encephalopathy” is defined as altered mental status as a result of a
diffuse disturbance of brain function.
 It represents a brain state in which normal functioning of the brain is disturbed
temporarily or permanently.
 Any clinical condition that causes impairment in consciousness usually
accompanied by diffuse EEG abnormalities

2. Types & Causes of encephalopathy
 Reversible
 metabolic encephalopathy,
 Hashimoto’s encephalopathy,
 hepatic encephalopathy,
 infectious of the brain,
 brain tumours,
 toxic encephalopathy,
 nonconvulsive status epilepticus
 Irreversible
chronic traumatic encephalopathy
Hypoxic-ischemic encephalopathy

3. Causes of encephalopathy
• Encephalopathy results main from,
• Metabolic derangements (Na, K, Ca)
• Toxins (exposure to toxic substances, e.g lithium paints, industrial
• chemicals)
• infectious (bacteria (TB) viruses, parasites, or prions),
• Hepatic (liver failure or liver cancer)
• Inflammations (Systemic Lupus Erythropetosis, sarcoidosis (soft
• tissues diseases)
• Drug Induced (Over dozage of the drug)
• Demyelinating (e.g MS)
• Degenerative processes (Alzheimer disease, Parkinson's disease)
• Anoxic encephalopathy (lack of oxygen to the brain, including
traumatic
• causes)
• Hereditary encephalopathies (leucodystrophy white matter)

4. SYMPTOMS
 Common symptoms
• confusion
• memory loss
• personality changes
• troubling in thinking or
focusing
 Less common symptoms
• trouble in speaking
• muscle weakness or twitches
• tremors
• seizures
• sleepiness

5. Hepatic encephalopathy
Definition: Hepatic encephalopathy is a reversible neuropsychiatric
state that complicates severe liver disease.
• Encephalopathy associated with Cirrhosis and portal hypertension
• Encephalopathy associated with portal systemic Bypass without
hepatocellular disease
• Encephalopathy associated with Acute liver failure

6. Clinical features
1. Disturbed consciousness:
Sleep disturbance (change of sleep pattern to hypersomnia , or
drowsiness ) Confusion including delirium Unconscious
2. Abnormal behavior
3. Intellectual deterioration (cognition)
4. Abnormal nerve reflexes Flapping tremor (asterixis)

7. Clinical grading
• Stage 1: Abnormal sleep, Abnormal behavior (mood change e.g.
euphoria/depression, strange behavior ) Altered cognition (
decreased attention and calculation ability) Flapping tremor (+/-) EEG
(+/-)
• Stage 2: Lethargic, Inappropriate behavior Disorientation and
memory decreased Flapping tremor (+), abnormal nerve
reflexes(ataxia) EEG (+) Clinical grading
• Stage 3: Somnolence but can be aroused, marked confusion
(delirium) Flapping tremor (+), abnormal nerve reflexes EEG (+)
• Stage 4: unconsciousness (can not be aroused) abnormal to loss of
reflexes

8. Investigation
• 1. Blood ammonia
• 2.Electroencephalogram
• 3. Evoked potentials
• 4. Psychometric tests

9. Treatment
. Identification & correction of the precipitating cause:
• Precipitating factors
• Drugs!
• Electrolyte imbalance – hypokalemia/metabolic alkalosis (diuretics,
vomiting, diarrhea, infusion)
• GI Bleeding Infection
• Constipation
• Large protein meal

10. Cont.
 Intervention to reduce the production & absorption of gut-derived
ammonia & other toxins:
• 1) Diet: reduce and modify dietary protein and maintain Calorie intake
• 2) Enemas (mild acid) and/or purgation
• 3) Lactulose or lactitol
• 4) Inhibition of gut bacteria: Antibiotics: neomycin(oral), metronidazone?
• 5) Modification of colonic flora: probiotics?
Modify colonic flora, resulting in displacement of urease-containing bacteria
with lactobacillus Cathartic effect
Lower the colonic pH, resulting in the formation of non-absorbable NH4
from NH3 in the colon

11. Metabolic encephalopathy
Pathophysiology:
• Mainly it depends on the cause However regardless the etiology the
main mechanism is due to disruption of arousal and attention centers
in the brain (ARAS).
• Another mechanism including compression or injury for areas critical
for memory ,attention and executive functions .
• Abnormalities in neurotransmitters such as ( (Ach , serotonin, GABA
,dopamine, tryptophan ,cytokines ) also affect these connections.

12. Uremic encephalopathy
Pathology :
• Decrease clearance of osmotically active toxins
• Proinflammatory state lead to BBB breakage
• Electrolytes abnormailites
• Seziures and myoclonus
• Dysequilibrium syndrome
• Dialysis dementia
• Cerebral atrophy

13. symptoms:
• Seizures and myoclonus
• Permanent memory loss
• Dysarthria
• Facial grimacing
• Myoclonus
• Mood and personality changes
• Confusion
• Headache
• Nausea and vomiting
• Tremors

14. Prognosis:
• Metabolic encephalopathy is common in the ICU setting
• the brain dysfunction that occurs with metabolic encephalopathy was
thought to be completely reversible
• critically ill patients with metabolic encephalopathy are often left
with long-term neurocognitive deficits.
• Persistent neurologic and psychiatric deficits occur in up to 32% of
medical ICU survivors

15. Management:
• Any of abnormal movement presented in renal patient should be
evaluated by EEG confirm diagnosis of myoclonus
• • Phenytoin used as AEDs in uremic patient to control sezuires but it
worse myoclonus
• • Best choice for myoclonus is tiratam &valporic acid

16. HASHIMOTO ENCEPHALOPATHY
• Defined by the detection of thyroid peroxidase (TPO) antibodies in
patients with acute or subacute encephalitis that responds to
steroids.
• “Encephalopathy associated with autoimmune thyroid disease” is
considered more accurate- due to normal thyroid function.
• Very vague symptoms- unclear course

17. Clinical features: non specific
• Stroke-like symptoms
• Tremor, myoclonus
• Transient aphasia
• Sleep and behaviour abnormalities
• Hallucinations, seizures and ataxia.

18. Diagnosis:
• clinical triad of neuropsychiatric symptoms, detection of antimicrosomal or
antithyroglobulin antibodies, and exclusion of other causes.
• antithyroid peroxidase, antithyroglobulin,
• lesser extent thyroid-stimulating hormone receptor
• blocking antibodies.
• α-enolase
• CSF show moderately elevated protein, may be positive for anti thyroid Ab, OCB
seen
• EEG: slowing, triphasic waves, epileptiform discharges.
• MRI usually normal, occasionally non-specific sub cortical white matter T2 signal
changes.
• Thyroid status may be normal.

19. Treatment:
• Initial treatment is usually with oral prednisone (50– 150 mg/day) or
high-dose IV methylprednisolone (1 g/day) for 3–7 days. Thyroid
hormone treatment is also included if required.
• Failure of some patients to respond to this first line treatment has
produced a variety of alternative treatments including azathioprine,
cyclophosphamide, chloroquine, methotrexate, periodic intravenous
immunoglobulin and plasma exchange.
• Seizures, if present, are controlled with typical antiepileptic agents.
• Recurrence – continued steroids, IVIG, other immunomodulatory
drugs.

20. NMDA ENCEPHALOPATHY
• Leading cause of autoimmune encephalitis in children and
adolescents.
• Age- frequently 2– 40 years, 80% Female
• Stages :
• Stage1 – prodromal phase
• Stage 2 – psychiatric and behavioral problems
• Stage 3 – Decreased level of consciousness
• Behavioral changes included new-onset temper tantrums, agitation,
aggression, and changes in mood or personality

21. Clinical features:
• Behavioural disturbance,Psychosis
• Catatonia
• Seizures
• Movement disorders including orolingual dyskinesias and stereotypic
movement.
• Dysautonomia.
• Ovarian teratoma is associated in up to 50% of the cases

22. Diagnosis
• CSF : -lymphocytic pleocytosis,
-elevated protein levels
-oligoclonal bands
• EEG – extreme delta brush
• MRI demonstrate medial temporal lobe attenuated inversion recovery
high signal or focal areas of hyperintensity in the frontal or parietal
cortex
• fluorodeoxyglucose positron emission tomography (FDG-PET) scan
show cortical hypermetabolism in acute stages, and hypometabolism
in more subacute stages of the illness.

23. Treatment
• first line of immunotherapies including corticosteroids, intravenous
immunoglobulin, or plasma exchange
• Rituximab and cyclophosphamide, alone or combined, are often
effective in adults
• Approximately 80% of patients have substantial or full recovery.

24. Septic encephalopathy
• The term "septic encephalopathy" :
• acute confusional episodes or other significant cognitive
abnormalities that develop during sepsis
• as an entity that cannot be explained by hepatic or renal dysfunction,
hypotension, or hypoxia
• Occur in a range of 8–70% of septic patients
• May as an early sign of sepsis
• Imply poor prognosis , higher mortality

25. Etiology and pathopysiology
• Most likely multifactorial
• Underlying mechanisms only been defined in parts
• Disseminated cerebral microabscesses
-infecting organisms and/or their toxins do not directly cause
encephalopathy.
• Systemic inflammation resulting from infection or other causes
action of inflammatory mediators on the brain , cytotoxic response of
brain cells

26. Cont.
• Free radicals
• damage RBC and limit O2 delivery to brain
• Inflammatory mediators
• impair mitochondrial function and O2 extraction by the brain
destroy BBB
• perimicrovessel edema
• disruption of astrocyte endfeet
• aromatic a.a enter brain parenchyma and disturb NT
• Ultimately, extensive neuronal injury

27. Diagnosis
No specific test available
Electroencephalopathy
• Most sensitive diagnostic tool
• Normal, diffuse slowing,excessive theta,predominantly delta,triphasic waves, and suppression or burst
suppression.
• Evaluating depressed consciousness in critically ill p`ts
• (1) Receiving sedative and narcotic drugs
• (2) Head injury , intracranial event e.g. cerebrovascular causes
• (3) Metabolic derangements :
• Sugar , electrolytes (Na ,Ca) , acid-base balance (acidemia , hypercapnia), oxygenation (hypoxia
,hypotention) , hepatic encephalopathy ,uremic encephalopathy , septic encephalopathy , alcohol or drug
• TREATMENT:
According to cause of septicemia
If hypotension start inotropic supports

28. Question.
• A 21-year-old primigravida with gestation age of 33weeks whose first
and second trimester gestation was uneventful with no history of
hypertension and epilepsy before and during pregnancy. She
developed sudden onset of headache, giddiness, vomiting, and
convulsions. Her blood pressure was 142/94 mmHg. Next day, the
patient was taken into C section for fetal distress. On 2nd day of
postcaesarean section she developed loss of vision, headache, and
vomiting. Her blood pressure was 140/114 mmHg.

29. PRES
• Posterior Reversible Encephalopathy Syndrome.
• Variety of symptoms – headache, altered mental status, visual
disturbances, and seizures.
• Hypertension, Pre-eclampsia/eclampsia, immunosuppression, sepsis,
chemotherapy, collagen vascular disease, and renal failure.

30. Question.
• A 36-year-old real estate agent was in the first trimester of her first
pregnancy when she awoke with diplopia. She had not been well for
several days, feeling lethargic, off-balance and slightly disoriented;
symptoms that she attributed to severe morning sickness during the
previous eight weeks. She was not taking any medications and had
been previously healthy. Exam revealed bilateral ptosis, limitation of
gaze in all directions, slow upward saccades, upbeat nystagmus and
mild ataxia.

31. • Wernicke’s encephalopathy –
• triad of ophthalmoplegia, ataxia, and confusion. O
• Triad – minority of cases. O
• Ocular findings – earliest and most constant. O
• About 30% have isolated or predominant mental status changes
ranging from confusion to frank coma. O
• Sometimes – sudden onset.

32. Mangement
• Low serum erythrocyte transketolase – days to obtain.
• Treat on suspicion.
• MRI – specific (93%) but sensitivity is low.

33. CNS infections/Para-infection

34. Clinical features:
• Fever , headache
• Meningism
• Focal neurological deficits
• Seizures
• Primary source of infection
• Pneumonia (bacteria, mycoplasma, TB), purpuric rash
(meningococcemia), mucosal herpetic lesions, cyanotic heart dis.
(brain abscess)

35. Investigations:
• CBC, CRP, ESR
• Blood culture
• Viral study (blood, throat, urine, stool)
• TB work-up
• CSF: ME, sugar, protein, C&S, virology, TB, fungus

36. Tumour /CNS Malignancy
• Suggestive features
• Signs & symptoms of raised ICP
• Focal neurological deficit
• Seizures
• Extra-cranial primary malignancy
• Neuro-imaging: 1 st line investigation

38. Toxic encephalopathy
• Toxic encephalopathy, also known as toxic metabolic encephalopathy,
is a degenerative neurologic disorder caused by exposure to toxic
substances.
• It can be an acute or a chronic disorder.
• Toxic encephalopathy can be caused by various chemicals, some of
which are commonly used in everyday life (paints, industrial
chemicals, and certain metals).

39. EEG in encephalopathy
In general,
• the most prominent feature of the EEG record in encephalopathies is
slowing of the normal background frequency.
• Reactivity to photic or other type of external stimulation may be
altered.
• Some conditions are associated with an increase in seizure frequency,
and in such cases, epileptic activity may be recorded.

40. EEG findings
• Triphasic has been associated with a wide range of toxic, metabolic,
and structural abnormalities.
• Triphasic waves are associated with an altered level of consciousness
that may range from mild confusion to deep coma.
• The background may be slower in hepatic failure
• A classic etiology of triphasic wave is hepatic/metabolic
encephalopathy.
• Triphasic’s are high-amplitude (>70 µV).
• Having three phase +ive, -ive and then +ive.
• Initial sharp component.

41. Clinical and electrographical features
• There is good correlation b/w the severity of the EEG changes , the severity of the
encephalopathy and the clinical state of the patient. *
• Degree of impairment is clinically categorized as—
• *Coma
• *Stupourous.
• *Lethargy/ hyper-somnia
• *Confusion
• *Delirium *
• Degree of impairment is Electrographically categorized as,
• 1.Background slowing without theta delta slow waves.
• 2.Diffuse theta delta activity associated with normal background activity.
• 3.Slow background activity with diffuse theta delta activity.

42. Clinical and electrographical features &
possible pathologies
• Background slowing--- cortical (gray matter) dysfunction
• Delta theta slow waves – (Brain) white matter disease
• Delta theta slow waves , along with slow background activity--- both
cortical and white matter disease
• Serial EEGs needed to evaluate the course of disease process

43. Grading of EEG abnormalities in diffuse
encephalopathy
• 1 a --slow background 7-8 Hz without theta delta waves
• 1b —4-6 Hz background without theta delta waves
• 2a —dominant theta delta with normal background activity.
• 2b —dominant theta delta with slow background activity
• 3a--dominant delta with normal background activity
• 3b—dominant delta with slow background activity
• 4a —moderate to high amplitude delta >50 microvolt with no background reactivity
• 4b —low amplitude < 5sec
• 5a —burst suppression with suppression period < 5sec
• 5b —burst suppression with suppression period >5 sec.
• 6a —near electro cerebral silence.
• 6b --ECS

44. Burst suppression pattern
• Recurrent, periodic or pseudo periodic bursts with EEG suppression
period of variable duration
• Burst can be a mixture of sharp, spike, alpha. theta, delta activities
• The suppression period can last from 2s to 20 mint.
• Seen in Anoxic brain damage, CNS supressant drugs and severe
hypothermia
• Paradoxical arousal response
• A stimulus brings out slower activity with generalized high voltage
delta bursts, that is called as paradoxical arousal response

45. Triphasic waves
• Typical and atypical--- *
• Typical –initial small negative sharp discharges of 2-4 Hz, followed by large
positive sharp discharge and subsequent negative wave. *Frontal
dominant, Continuous, stereotyped ,forms a phase lag from anterior to
posterior region, seen in hepatic encephalopathy. *
• Atypical—less continuous, less stereotyped ,present in uremic,
hyperthyroid, toxic encephalopathies
• *In dementia (AD) posterior dominant triphasics are present.
• TW are also seen in encephalopathies associated with renal failure or
electrolyte imbalance, as well as anoxia and intoxications (such as lithium,
metrizamide, and levodopa)

46. ECS
• *No EEG activity over 2 micro volts when recorded from scalp
electrode pairs 10 cm interelectrodes distance.
• *Filter settings should not b below 30 Hz and low filter should not be
higher than 1 Hz.
• *Recording should be at-least one hour, with artifacts free 30 min
recording on 2uv.
• *Electrodes impedance should be 100ohm to 10Kohm.

47. References
• Practical Guide for Clinical Neurophysiologic Testing: EEG: Thoru
Yamada MD.
• *Basic Principles, Clinical Applications, and Related Fields
• *By Ernst Niedermeyer
• nelson text book of paediatrics 19th edition

48. Hashimoto’s Encephalopathy
• Steroid responsive acute or subacute encephalopathy associated with
anti-thyroid antibodies.
• Presenting features vary widely.
• Psychiatric symptoms around 60%.
• TPO and Thyroglobulin.
• TSH should be high but patients may be euthyroid or hypothyroid.
• Myxedema coma – acute or subacute and precipitated by stress.
• Hypothermic, Hypo ventilate, and “suspended animation.”

49. Hyper-Hypoglycemia
• Hyperosmolality
• Diabetic ketoacidosis – pH doesn’t correlate well with level of
consciousness.
• Diabetic lactic acidosis.
• Sudden lowering of serum osmolality – cerebral edema – can be fatal.
• Head trauma and Stroke patients – Glucose control.

50. Hypoglycemia
• Stroke like illness.
• Delirium.
• Coma.
• Seizure.
Hyperglycemia
• Seizures
• Hemianopia
• Hemichorea/Hemiballismus

51. Hypoglycemic Brain Injury
• Range from reversible focal deficits and transient encephalopathy to
irreversible coma.
• Mean blood glucose was around 30mg/dl.
• White matter – more sensitive to ischemia than previously thought.
• The duration of hypoglycemia may be difficult to determine in many
cases.

52. Hypoxic ischemic encephalopathy
• Abnormal neurological behaviour in the neonatal period arising as a
result of a hypoxic-ischemic event.
• Occurs in1-6 per 1000 term live births in developed countries
• 25% die or have multiple disabilities
• 4% have mild to moderate forms of cerebral palsy
• Essential criteria for diagnosis of HIE:
- metabolic acidosis
-early onset of encephalopathy
-Multisystem organ failure

54. Diagnosis
• Mri is the preferred imaging modality in neonates with HIE
• CT scan : identifies focal hemorrhagic lesions, diffuse cortical injury
and damage to the basal ganglia.
• aEEG : determine which infant are at high risk for long term brain
injury.
Treatment
1.hypothermia
2.Drug therapy : phenobarbital,phenytoin
3. Supportive care

55. WERNICKE ENCEPHALOPATHY
• WE is an acute, potentially reversible, neuropsychiatric disorder
caused by thiamine deficiency.
• The incidence can be as high as 12.5%
• The altered cognition of WE can progress to KS, a chronic and usually
permanent.
• Approximately 80% of patients with acute WE will develop KS.
• Mechanism:- Chronic alcoholism – Malnutrition – reduced thiamine
uptake and utilization

56. Physical examination
• The classical triad of symptoms – only 1/3rd of cases
• Ocular abnormalities – nystagmus, bilateral lateral rectus palsies,
conjugate gaze palsies, sluggish pupils, ptosis, and anisocoria
• Encephalopathy – global confusionalstate, disinterest,
inattentiveness, or agitation; Coma is rare.
• Gait ataxia – cerebellar damage, and vestibular paresis
• Peripheral neuropathy – foot drop, and decreased proprioception

57. Management
• Erythrocyte transketolase activity assay, Thiamine assay – very specific tests – not widely
available – reserved for diagnostic dilemmas
• EEG and CSF analysis may exclude other explanatory or concomitant conditions.
• Emergency department care – Parenteral thiamine –Requirement in chronic alcoholics
may be as high as 500mg single dose or multiple daily doses.
• Never start on Dextrose
• Treatment with thiamine repletion, currently recommended at 1 gram of IV thiamine per
24 hours for alcoholics with suspected Wernicke encephalopathy , should not be delayed.
• Death occurs in nearly 20 % of patients with delayed treatment.
• In-Patient care –Watch for complications – Korsakoff psychosis –Alcohol withdrawal –
Congestive heart failure – Lactic acidosis
• Out-Patient Care – Thiamine 100 mg PO daily, start alcohol cessation program, Advise on
importance of balanced diet.

58. Refrences
• Practical Guide for Clinical Neurophysiologic Testing: EEG: Thoru
Yamada MD.
• Basic Principles, Clinical Applications, and Related Fields
• By Ernst Niedermeyer
• nelson text book of paediatrics 19th edition

59. Thank you