Seizures

Causes:

• Idiopathic epilepsy
• Head injury
• Congenital cerebral defects
• Cerebral abscess, meningitis, tuberculoma, encephalitis, cerebral malaria
• Cavernous sinus thrombosis
• Febrile convulsions
• Pyridoxine deficiency
• Hypoglycemia
• Hypoxia
• Intracranial space occupying lesion
• Acute poisoning
• Infections
• Hyponatremia
• Hypocalcemia
• Uremia
• Eclampsia
• Degenerative brain disease
• Drugs
• Posterior reversible encephalopathy syndrome

Evaluation:

• History and examination
• Blood sugar levels
• Send: CBC, PT, APTT, RFT, LFT, Electrolytes
• Drug and alcohol screen
• ABG
• Blood culture
• ECG
• Chest X Ray
• CT/MRI of brain

Treatment:

• High dose O2 by face mask
• Inj. Midazolam- 0.05-0.1mg/kg- IV up to 10mg  /  Inj. Lorazepam- 0.07mg/kg- up to 4 mg- IV
• If seizures do not stop- Midazolam infusion- 0.05mg/kg/hr
• Inj. Levetiracetam- 500mg- in 100ml NS- IV- BD

Altered Consciousness/ Unconscious Patient

Causes:

• Severe infection
• Cerebral malaria
• Meningitis
• Encephalitis
• Cerebral tumor
• Hypoglycemia
• Diabetic ketoacidosis
• Uremia
• Poisoning- Drugs, Alcohol
• CCF, MI
• Severe anemia
• Cerebrovascular accident
• Brainstem lesion: tumor, hemorrhage, demyelination
• Head injury- Concussion, hematoma
• Hepatic failure
• Uremic encephalopathy
• Metabolic acidosis
• Hyponatremia
• Hyperosmolarity
• Hypercalcemia
• Postepileptic coma
• Hypertensive encephalopathy
• Heat stroke
• Wernicke's encephalopathy
• Hyper/Hypothyroidism
• Psychogenic unresponsiveness
• CO2 Narcosis, Hypoxia

Glasgow Coma Scale (E_M_V_)

• Eye Opening (E)
  • 4- Spontaneous
  • 3- To speech
  • 2- To pain
  • 1- No Response
• Motor Response (M)
  • 6- Obeys
  • 5- Localizes
  • 4- Withdraws
  • 3- Abnormal flexion
  • 2- Extensor response
  • 1- Nil
• Verbal Response (V)
  • 5- Oriented
  • 4- Confused conversation
  • 3- Inappropriate words
  • 2- Incomprehensible sounds
  • 1- Nil

Evaluation:

• History and examination
• Blood glucose using glucometer
• Hemogram, RFT, LFT, PT, APTT, Electrolytes, S. Lactate, Ammonia, ABG
• Blood for drug level estimation/ choline esterase
• Blood culture
• Malaria by QBC
• Urine routine
• Chest X Ray
• USG abdomen
• ECG
• CT/ MRI Brain
• Lumbar puncture

Treatment:

• 50% Dextrose- 50ml with Thiamine 100mg- over 30min- Give irrespective of cause
• Treatment of cause
  • Ryle's tube insertion. Stomach wash if poisoning
  • Catheterize bladder
  • Intubation for airway protection
  • Start RT feeds
  • Eye shield and Neosporine ointment- To prevent exposure keratitis
  • Prevent bed sores- 2nd hrly change of position, Nurse on air/water bed
  • Chest physiotherapy
  • Intermittent throat suction to clear secretions/ Care of ET tube, periodic sterile suction

Epidural/ Spinal Cord Compression

If identified early patient may be spared of significant disability

Causes:

• Metastatic malignancy, lymphoma, myeloma, sarcoma- most commonly in thoracic spine
• Tuberculosis, osteomyelitis
• Epidural hematoma
• Herniated intervertebral disc

Clinical features:

• Backache
  • Frequently referred/ radicular pain
  • Unlike prolapsed disc, pain is exacerbated by recumbency and is improved by up-right position 
• Weakness and Sensory impairment
  • Follows within hours to weeks after onset of back pain
  • Begins in proximal legs
  • Can progress to paraplegia
• Autonomic dysfunction- Bladder, Bowel dysfunction

Investigations:

• Whole spine MRI
• CT Myelography, if MRI is contraindicated
• CT or MRI guided biopsy

Treatment

• Immediate hospitalization
• Analgesics for pain control
• Inj. Dexamethasone- 8 mg- 6th hrly- Start immediately after the diagnosis is suspected. Do not wait for imaging reports.
• Immediate neurosurgery consultation for decompression procedure and / or stabilization of spine.
• Radiation-
  • Either in lieu of surgery or after surgery
  • 10 uninterrupted fractions of 3 Gray each
  • RT must be started within 24hrs of onset of symptoms

Methotrexate Induced Encephalopathy

• Stroke like acute neurotoxicity
• Often secondary to decreased renal function which leads to decreased elimination of methotrexate
• Treatment:
  • Inj. Aminophylline- 2.5mg/kg IV infusion over 60min
  • Inj. Folinic acid
• Usually full recovery is seen

Idiopathic Hyperammonemia

• Seen 2.4% of leukemia treated patients and 1.2% of patients undergoing stem cell transplant.
• Mortality- 75%
• Risk factors:
  • Catabolic state
  • Total parenteral nutrition
  • GI hemorrhage
  • Infections
• Clinical features
  • Progressive encephalopathy
  • Tachypnea
• Investigations
  • LFT- Normal
  • Respiratory alkalosis due to hyperventilation
  • S. Ammonia levels- >2folds the upper limit of normal and  rising
• Other causes of encephalopathy have to be excluded- Reye's syndrome, port-systemic shunt, fulminant hepatitis, cirrhosis, veno occlusive disease, hypoglycemia etc
• Rule out drug induced hyperammonemia- Sodium valproate, L-asparaginase
• Treatment:
  • Should be started immediately, otherwise irreversible brain damage ensures
  • Stop protein supplementation. Later on 2% solution of essential amino acids (valine, leucine and isoleucine) may be provided.
  • Calories- 100-200kCal/kg/2hrs- With 10% glucose with insulin (1unit/4gm of glucose)
  • Increase ammonia secretion- Arginine, sodium benzoate, sodium phenyl acetate
  • Identify and treat GI bleed
  • Lactulose- 20ml- 6hrly
  • PO- Neomycin- 50-100mg/kg/day
  • Hemodialysis
  • Mechanical ventilation if altered sensorium/ cerebral edema
  • Monitor electrolytes

Posterior Reversible Encephalopathy Syndrome and Hypertensive Emergencies

Introduction:

• It is a condition characterized by variable association of 
  • Seizure activity
  • Consciousness impairment/ confusion/ coma
  •  Headache
  • Visual abnormalities: Blurred vision, visual neglect, homonynoushemianopia, visual hallucinations, cortical blindness
  • Nausea, vomiting
  • Hypertension- Often present

Epidemiology:

• Age: 4-90 years, most cases in young and middle age
• Marked female predominance

Etiology:

• Toxic agents:
  • Chemotherapy agents: Cisplatin, oxaliplatin, carboplatin, gemcitabine, cytarabine, methotrexate, vincristine, L-asparaginase
  • Anti-angiogenic agents: Bevacizumab, sunitinib, RAF kinase inhibitors
  • Immunomodulatory cytokines: Interferon alpha, IL 2
  • Monoclonal antibodies: Rituximab, Infliximab
  • IV Immunoglobulin
  • Anti TNF alpha- Etanercept
  • Anti lymphocyte globulin
  • Immunosuppressive agents: Cyclosporine, tacrolimus, sirolimus
  • High dose corticosteroids
  • Others- G-CSF, ART, Linezolid, EPO, IV Contrast agents, Carbamazepine
• Hypertension
• Infections and sepsis
• Pre-eclampsia and eclampsia
• Autoimmune disorders: SLE, PAN, Wagener's granulomatosis, thrombotic micro-angiopathy, systemic sclerosis, Takayasuarteritis, Hashimoto encephalopathy, Crohn disease
• Others: Sickle cell disease, GBS, Hypomagnesemia, hypercalcemia, tumor lysis syndrome, porphyria, pheochromocytoma, Cushing syndrome

Pathogenesis:

2 hypotheses

• Impaired cerebral autoregulation leading to increased cerebral blood flow. This leads to cerebral edema
• Endothelial dysfunction with release of proinflammatory cytokines. This causes increased vascular tone and subsequent cerebral hypoperfusion

Investigations:

• MRI combined with MRA:
  • Bilateral symmetric regions of edema typically located in the white matter and predominating posterior parietal and occipital lobes
  • T2 weighted images show areas of high signal intensity
  • Fluid attenuated inversion recovery (FLAIR) also visualize the lesions
  • Other associated abnormalities that can be seen are: cerebral ischemia, hemorrhage, herniation
• EEG: To be done to look for non convulsive status epilepticus
• Lumbar puncture and CSF analysis
• Neurosurgical biopsy: If patient fails to respond to appropriate therapy

Differential diagnosis:

• Ictal/ post-ictal phase
• Progressive multifocal leuco-encephalopathy
• CADASIL
• Infectious encephalitis
• Acute disseminated encephalomyelitis
• MELAS
• Vasculitis
• Creutzfeldt Jacob disease
• Cerebral venous sinus thrombosis
• Ischemic stroke

Prognosis:

• With appropriate treatment there is full recovery. But sometimes permanent complications/ fatalities are observed.

Treatment:

• Admit in ICU, ionotropic support if needed, endotracheal intubation to protect airway
• Look for hypoglycemia and treat accordingly (Give thiamine along with glucose)
• Look for hypomagnesemia and treat promptly
• Antiepileptics: Clonazepam 1mg- Repeat up to 3 times if necessary, followed by Levetiracetam
• Control of hypertensive emergency
  • Aim should not be to normalize BP but reduce mean arterial pressure by 20-25% within first 2 hrs, then bring down BP to 160/100 mm of Hg within 1st 6 hrs. More rapid reduction promotes ischemia.
  • Inj. Labetalol/ Nicardipine
• Correction of underlying causes of PRES
  • BP Control
  • Withdrawal of cancer chemotherapy/ immunosuppressant
  • Termination of pregnancy
  • Dialysis