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Conditions of the Neurological System

Conditions of the Neurological System. Part A: Module A2 Session 4. Objectives . Describe the various etiological agents that cause neurological disorders Give key points when taking a history Describe the clinical presentation of each disorder

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Conditions of the Neurological System

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  1. Conditions of the Neurological System Part A: Module A2 Session 4

  2. Objectives • Describe the various etiological agents that cause neurological disorders • Give key points when taking a history • Describe the clinical presentation of each disorder • List the recommended diagnostics and common findings for each disorder • Understand the treatment and management of neurological disorders • Discuss preventive measures • Make a differential diagnosis using a case study approach

  3. Overview • Reported incidence of neurological abnormalities on clinical examination varies greatly, from 16% to 72% among hospitalized patients • A wide range of neurological manifestations is reported: cognitive defects, focal deficits such as hemiplegia and acute peripheral facial palsy, painful feet syndrome, encephalopathy • Some of these manifestations are directly caused by HIV itself, others are the result of OIs caused by different pathogens or drugs

  4. Major Pathogens Protozoal infectionToxoplasma Gondii (toxoplasmosis) Mycobacterial infectionM. tuberculosis (TB meningitis) BacterialStrep pneumoniae, Neisseria meningitis (bacterial meningitis) FungalinfectionCryptococcus neoformans (cryptococcal meningitis) ViralinfectionCytomegalovirus (CMV) Other:Progressive multifocal leukoencephalopathy (PML) Primary CNS lymphoma • HIV-associated dementia (HAD) • Painful sensory and motor peripheral neuropathies • Neurosyphilis

  5. Chart 2. Conditions of the Neurological System

  6. Protozoal infection: Toxoplasma Gondii (toxoplasmosis)Presenting Signs and Symptoms • Clinical symptoms may evolve • Focal neurological deficits, e.g., seizures, hemiparesis, hemiplegia, cerebellar tremor, cranial nerve palsies, hemisensory loss, visual problems or blindness, personality changes, cognitive disorders • Headache (severe, localized) • Fever • Confusion • Myalgia • Arthralgia

  7. Diagnostics • CSF values • Normal: 20-30% • Protein: 10-150/ml • WBC: 0-40 (monos) • Blood: FBC ***** An HIV-infected individual presenting with typical signs and symptoms and normal cerebrospinal fluid findings should be put on treatment for toxoplasmosis

  8. Cerebral toxoplasmosis

  9. Management and Treatment • Provide physiotherapy as necessary • Start anti-convulsant treatment • Epanutin 50 – 100 mg bid or tid or tegretol 100 – 200 mg bid or tid (to be started only if the patient has convulsion)

  10. Management and Treatment, continued • Start Treatment for acute phase: • Pyrimethamine 100 – 200 mg loading dose, then 50 – 100 mg/day po + folinic ( or folic) acid 10 mg/day po + sulfadiazine 1-2g qid for at least 6 weeks or • Trimethoprim/Sulfamethoxazole (10/50mg/kg daily) for 4 weeks or • Clindamycin (600mg tid) + pyrimethamine 100mg daily loading dose followed by 50 mg daily + folinic acid 10 mg daily

  11. Unique features, Caveats • One of the most common HIV-related neurological complications • If patient does not receive maintenance therapy, disease will recur. Usually occurs when CD4<100 • Check blood picture regularly as relatively high doses of drugs can lead to toxicities • Leukopenia thrombocytopenia and rash are common. Folinic acid reduces the risk of myelosuppression • During treatment, patients should maintain a high fluid intake and urine output • Preventive measures and prophylaxis: See Part One, Module 2/Session 10

  12. Treatment after a case of Toxo • Preferred regimen for suppressive therapy required after a patient has had Toxo: • Pyrimethamine 25-75 mg po qd + folinic acid 10 mg qd + sulfadiazide 0.5-1.0 gm po qid If allergic to sulfa • Give Dapsone po 100 mg po once daily or Clindamycin IV (or oral) 600 mg qid or Atovaquine 750 mg po qid

  13. Mycobacterial Infection: M. tuberculosis (TB Meningitis) Presenting Signs and Symptoms • Gradual onset of headache and decreased consciousness • Low grade evening fevers • Night sweats • Weight loss • Neck stiffness and positive Kernig’s sign • Cranial nerve palsies result from exudate around base of the brain

  14. Diagnostics • CSFValues • Normal: 5-10% • Protein: High (40mg/dl-100 mg/dl) • WBC: 5-2000 (average is 60-70% monos) • Glucose: low (<20 mg/dl) • AFB smear pos: 20%

  15. Unique features, Caveats • CD4<350 • Up to 10% of HIV/AIDS patients who present with TB will show involvement of the meninges. This results either from the rupture of a cerebral tuberculoma or it is blood-borne • Always exclude cryptococcal meningitis by CSF microscopy (India ink stain)

  16. Bacterial Infection: Strep pneumoniae, Neisseria Meningitis (Bacterial Meningitis)Presenting Signs and Symptoms • Symptoms tend to present within one week of infection. May be preceded by a prodromal respiratory illness or sore throat. - Fever - Vomiting - Headache - Malaise - Stiff neck - Irritability - Photophobia - Drowsiness - Coma

  17. Diagnostics • CSF Values • leukocytosis • cerebrospinal fluid shows increased pressure • cell count (100 –10,000/mm3) • protein (>100 mg/dl) • decreased glucose (<40 mg/dl or <50% of the simultaneous glucose blood level) • gram-stained smear of the spun sediment of the CSF can reveal the etiologic agent

  18. Management and Treatment • Penicillin (24 million units daily in divided doses every 2-3 hours) or • Ampicillin (12 gr daily in divided doses every 2-3 hours) or • Chloramphenicol (4 to 6 grams IV/day). Treatment should be continued for 10 to 14 days. Crystalline penicillin 2-3 mega units and chloramphenicol 500-750 mg every 6 hours for 10-14 days

  19. Unique features, Caveats • Often encountered during late stages of HIV disease. Prompt diagnosis and aggressive management and treatment ensure a quick recovery

  20. Fungal Infection: Cryptococcus neoformans(cryptococcal meningitis)Presenting Signs and Symptoms • Presentation usually nonspecific at onset. This may be true for > 1 month. • Protracted headache and fever may be the only signs • Nausea, vomiting, and stiff neck may be absent and focal neurological signs uncommon. • Extraneural symptoms: - skin lesions, pneumonitis, pleural effusions and retinitis • Fever, malaise, nuchal pain signify a worse prognosis, and nausea and vomiting and altered mental status in terminal stages

  21. Diagnostics • CSF Values • Normal 20% • Protein 30-150/dl • WBC: 0-100 (monos) • Glucose decreased: 50-70mg/dl • Culture positive: 95-100% • India ink positive: 60-80% • Crypt Ag nearly 100% sensitive and specific

  22. Cryptoccocal meningitis: CSF Indian ink examination

  23. Management and Treatment • Preferred regimen: • Amphotericin P 0.7 mg/kg/day IV, + flucytosine 100 mg/kg/day po x 14 days, followed by Fluconazole 400 mg/day x 8-10 weeks. Finally, maintenance therapy with Fluconazole 200mg/day for life

  24. Management and Treatment, continued • Alternate regimen: • Amphotericin B 0.7 mg/kg/day IV + flucytosine 100mg/kg/day po x 14 days followed by itraconazole 200mg bid for 8 weeks • Fluconazole 400 mg/day po x 8 weeks followed by 200 mg once daily • Itraconazole 200 mg po tid x 3days, then 200 mg po bid x 8 weeks after initial treatment with amphotericin • Fluconazole 400 mg/day po + flucytosine 100 mg/kg/day po

  25. Unique features, Caveats • If untreated, it is slowly progressive and ultimately fatal • Most common life-threatening fungal infection in HIV/AIDS patients. Also the most common cause of meningitis in patients with HIV/AIDS in Africa and Asia. Occurs most often in patients with CD4<50 It is better prevented than treated

  26. Unique features, Caveats, continued • Headache is secondary to fungal accumulation. Headache increases gradually over time and then follows a recurring pattern. It becomes harder to get rid of, and then becomes continuous. This is what the patient reports. • Requires lifelong suppressive treatment unless immune reconstitution occurs

  27. Viral Infection: Cytomegalovirus (CMV)Presenting Signs and Symptoms • Fever  delirium, lethargy, disorientation, malaise, headache most common • Stiff neck, photophobia, cranial nerve deficits less common • No focal neurological deficits • Gastrointestinal symptoms: diarrhea, colitis, esophageal ulceration appear in 12-15% of patients • Respiratory symptoms, i.e, pneumonitis, present ~1%

  28. Diagnostics • Retinal exam to check for changes. Consult an ophthalmologist • CMV retinitis, characterized by creamy yellow white, hemorrhagic, full thickness retinal opacification, which can cause visual loss and lead to blindness if untreated; patient may be asymptomatic or complain of floaters, diminished acuity or visual field defects. Retinal detachment if disease is extensive • UGI endoscopy when indicated

  29. Management and Treatment • Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h x 14-21 days; ganciclovir 5mg/kg IV bid x 14-21 days. Patients without immune recovery will need to be on maintenance therapy lifelong for retinitis • Extra-ocular; ganciclovir and/or foscarnet

  30. Unique features, caveats • Evolution occurs in less than 2 weeks • Usually when CD4<100 • Although any part of the retina may be involved, there is a predilection for the posterior pole; involvement of the optic nerve head and macula region is common • Characteristically involves the retinal vessels which are always abnormal in areas involved by retinitis. There is minimal or no accompanying uveitis • Rare but devastating illness in resource poor settings. Treatment is very expensive and usually not available. CMV management needs special care. Therefore, early referral is essential

  31. Viral Infection: Progressive mulltifocal leukoencephalopathy (PML)Presenting Signs and Symptoms • Afebrile, alert, no headache • Progressively impaired speech, vision, motor function • Cranial nerve deficit and cortical blindness • Cognition affected relatively late

  32. Diagnostics • CT brain scan may be normal or remarkable for areas of diminished density or demyelination (deterioration of the covering of the nerve) • PCR of CSF for detection of JC virus • JC virus PCR is positive in about 60% of the cases • Differential diagnosis: • Toxoplasmosis • Primary CNS lymphoma • Definitive diagnosis is by brain biopsy (if available)

  33. Management and Treatment There is no treatment for this illness ART can improve symptoms and prolong life

  34. Unique features, Caveats • An end-stage complication of HIV, caused by the JC virus • PML is rare in the general community, but relatively common in HIV infection (affecting 4% of all AIDS patients). Routine testing for HIV should be considered for any patient with PML • Evolution occurs over weeks to months • CD4<100

  35. Primary CNS lymphomaPresenting Signs and Symptoms • Disease progresses slowly over a few weeks • Afebrile • Headache • Focal and multifocal neuro deficits (confusion, hemiplegia, seizures) • Mental status change (60%), personality or behavioral • Seizures (15%)

  36. Cerebral lymphoma

  37. Diagnostics • CT Scan/MRI • Location: pre-ventricular in one or more site • Prominent edema, irregular and solid on enhancement. • CSF: • Normal;—30-50% • Protein—10-150/ml • WBC—0-100 (monos) • Cytology positive in <5% • Suspect with negative toxo IgG or failure to respond to empiric toxo treatment

  38. Management and Treatment • There is no cytotoxic chemotherapy for this disease. Irradiation can help some patients, but is considered palliative  • Corticosteroids can also help some patients

  39. Unique features, Caveats • Primary CNS Lymphoma is RARE in the general community, but affects about 2% of AIDS patients • Survival after diagnosis is usually limited (a few months only) • Typical end-stage complication of HIV disease • Evolution: 2-8 weeks • Usually occurs when CD4<100

  40. HIV-associated dementia (HAD) Presenting Signs and Symptoms • In up to 10% of patients it is the first manifestation of HIV disease • Afebrile; general lethargy • Triad of cognitive, motor and behavioral dysfunction • Early - concentration and memory deficits, inattention, motor-uncoordination, ataxia, depression, emotional lability • Late - global dementia, paraplegia, mutism

  41. Diagnostics • Neuropsychological tests show subcortical dementia • Mini-mental exams not very sensitive

  42. AIDS dementia complex

  43. Management and Treatment • Possible benefit from ARV agents that penetrate the CNS (AZT, d4T, ABC, nevirapine) • Benefit of AZT at higher dose for mild or moderately severe cases is established; monitor therapy with neurocognitive tests • Anecdotal experience indicates response to ART if started early

  44. Management and Treatment, continued • Sedation for those who are agitated and aggressive—use smaller doses initially to avoid over-sedation • Close monitoring: to prevent self-harm, ensure adequate nutrition, diagnose and treat OIs early • Psychological support for caregivers—exhausting work; caregivers need regular breaks and may need counseling

  45. Painful Sensory and Motor Peripheral Neuropathies Presenting signs and symptoms • Burning pain and numbness in toes and feet, ankles, calves, fingers in more advanced cases • Paraplegia • Autonomic dysfunction • Poor bowel/bladder control • Dizziness secondary to postural hypotension • Contact hypersensitivity in some cases • Mild/moderate muscle tenderness • Muscle weakness • Later: Reduced pinprick/vibratory sensation; reduced or absent ankle/knee jerks • Sweating

  46. Diagnostics • Electromyography/nerve conduction velocities show predominantly axonal neuropathy • CPK usually elevated • CSF - look for cytomegalovirus or herpes simplex virus infections—lymphomatous infiltration • Spinal fluid to determine etiology • Serum B12 and TSH • Quantitative sensory testing or thermal thresholds may be helpful

  47. Management and Treatment • Exclude neurotoxic drugs, alcoholism, diabetes, B12 deficiency, thyroid problems and treat underlying causes if known. • Discontinue presumed neurotoxic medication • Provide proper nutrition and vitamin supplements

  48. Management and Treatment, continnued • Pain control: • Ibuprofen 600-800 mg po tid or codeine for modest symptoms • Amitryptiline 25-50 mg at night • Phenytoin 50-100 mg bid or carbamazapine 100-200 mg tid– especially for episodic shooting pain. May have to combine antidepressants with anti-convulsants • Methadone or morphine for severe symptoms • Lidocaine 10-30% ointment for topical use • Physical therapy may be helpful, but may be hampered by pain • Nutrition counseling and psychological support

  49. Unique features, Caveats • Differential: toxoplasmosis, primary CNS lymphoma  • Management and treatment is difficult. • Consider physical therapy combined with pain management.

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