| 7.1. Myasthenia gravis |
Work-up and evaluation: - AChR and antistriated muscle antibodies in blood. If AChR antibodies are negative, consider MuSK and LPR4 antibodies in blood – while presence of antibodies is confirmatory, the absence of antibodies does not rule out the syndrome.
- Pulmonary function assessment with NIF and VC.
- CPK, aldolase, ESR, and CRP for possible concurrent myositis.
- Consider MRI brain and/or spine depending on symptoms to rule out CNS involvement by disease or alternate diagnosis.
- Troponin, ECG, and consider TTE and/or cardiac MRI to evaluate concomitant myocarditis.
- Electrodiagnostic studies, under neurologic consultation, including neuromuscular junction testing with repetitive stimulation and/or jitter studies, NCS to exclude neuropathy, and needle EMG to evaluate for concomitant myositis.
- Inflammatory markers (ESR and CRP).
- Consider paraneoplastic work-up.
- Review and stop medications with known risk of worsening myasthenia: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics.
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| Grading | Management |
| All grades. | - All grades warrant work-up and intervention given potential for progressive MG to lead to respiratory compromise. Inpatient admission may be appropriate at all grades.
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| No G1. | |
| G2: Some symptoms interfering with ADLs. MGFA severity class I (ocular symptoms and findings only) and MGFA severity class II (mild generalized weakness). | - Hold ICPi and may resume in G2 patients (MGFA 1 and 2) only if symptoms resolve and steroid taper completed.
- Neurology consultation.
- Strongly consider inpatient care as patients can deteriorate quickly.
- Pyridostigmine starting at 30 mg orally three times a day and gradually increase to maximum of 120 mg orally four times a day as tolerated and based on symptoms and wean based on improvement. These procedures should be done in close collaboration with the neurologist.
- Administer corticosteroids (prednisone 0.5 mg/kg¶ orally daily). Wean based on symptom improvement.
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| G3-4: Limiting self-care and aids warranted, weakness limiting walking, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms or MGFA severity class III-V (moderate to severe generalized weakness to myasthenic crisis). | - Follow G2 recommendations as listed, with the following additions for G3-4:
- Permanently discontinue ICPi.
- Admit patient, may need ICU-level monitoring.
- Continue steroids, taper should begin 3 to 4 weeks after initiation then wean based on symptom improvement.
- Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 5 days.
- Consider adding rituximab if refractory to IVIG or plasmapheresis.
- Frequent pulmonary function assessment.
- Daily neurologic review.
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| 7.2. Guillain-Barré syndrome |
Work-up and evaluation: - Neurologic consultation.
- MRI spine with or without contrast (rule out compressive lesion and evaluate for nerve root enhancement/thickening).
- Lumbar puncture: CSF analysis for cell count and differential, cytology for malignant cells, protein, glucose, and viral/bacterial cultures. Note that CSF typically has elevated protein and often elevated WBC as well, although this is not typically seen in classical Guillain-Barre.
- Consider paraneoplastic work-up eg ANNA-1 antibody testing.
- Serum antiganglioside antibody tests for GBS and its subtypes (eg, anti-GQ1b for Miller Fisher variant associated with ataxia and ophthalmoplegia).
- Flow cytometry in patients with hematologic malignancies.
- Electrodiagnostic studies (NCS and EMG) to evaluate polyneuropathy.
- Pulmonary function testing (NIF or VC).
- Frequent neuro checks.
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| Grading | Management |
| All grades warrant work-up and intervention given potential for progressive GBS to lead to respiratory compromise. NOTE: there is no G1 toxicity. |
| No G1. | |
G2: Moderate: Some interference with ADLs, symptoms concerning to patient.
G3-4: Severe: Limiting self-care and aids warranted, weakness limiting walking, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms. | - Discontinue ICPi.
- Neurology consultation.
- Admission to inpatient unit with capability of rapid transfer to ICU-level monitoring.
- Start IVIG (0.4 g/kg/day for 5 days for a total dose of 2 g/kg) or plasmapheresis. NOTE: plasmapheresis immediately after IVIG will remove immunoglobulin.
- Corticosteroids are usually not recommended for idiopathic GBS; however, in ICPi-related forms, a trial is reasonable (methylprednisolone 2 to 4 mg/kg/day), followed by slow steroid taper. Pulse steroid dosing (methylprednisolone 1 g daily for 5 days) may also be considered for G3-4 along with IVIG or plasmapheresis. After pulse steroids, taper steroids over 4 to 6 weeks.
- Frequent neuro checks and pulmonary function monitoring.
- Monitor for concurrent autonomic dysfunction.
- Nonopioid management of neuropathic pain, for example, pregabalin, gabapentin, or duloxetine.
- Treatment of constipation/ileus.
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Additional considerations: - Extreme caution with rechallenging for severe cases after complete resolution of symptoms and tapered off immunosuppression.
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| 7.3. Peripheral neuropathy |
Work-up and evaluation: - G1:
- Consider neurology consultation to guide neuropathy phenotype determination and work-up.
- Serum testing for reversible neuropathy causes: HbA1c, vitamin B12, TSH, vitamin B6, folate, serum protein electrophoresis, and immunofixation, CPK.
- Consider additional testing guided by neuropathy phenotype: ANA, ESR, CRP, ANCA, anti–smooth muscle, SSA/SSB, RNP, anti-dsDNA, ganglioside ab, anti-MAG, anti-Hu (ANNA-1 ab), thiamine, Lyme, hepatitis B or C, and HIV.
- Consider MRI spine with or without contrast.
- G2 – in addition to the above:
- MRI spine advised, MRI brain if cranial nerve involvement, and MRI plexus if concern for plexus involvement.
- Consider lumbar puncture: CSF analysis for cell count and differential, cytology for malignant cells, protein, glucose, and viral or bacterial cultures. Consider EMG or NCS.
- G3-4: Refer to section 7.2 on management of grade 3-4 GBS.
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| Grading | Management |
| G1: Mild: no interference with function and symptoms not concerning to patient. NOTE: any cranial nerve problem should be managed as moderate. | - Low threshold to hold ICPi and monitor symptoms for a week. If to continue, monitor very closely for any symptom progression.
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| G2: Moderate: some interference with ADLs, symptoms concerning to patient (ie, pain but no weakness or gait limitation). | - Hold ICPi and resume once return to ≤G1.
- Initial observation or initiate prednisone 0.5 to 1 mg/kg/day (if progressing from mild).
- Gabapentin, pregabalin, or duloxetine for pain.
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| G3-4: Severe: limiting self-care and aids warranted, weakness limiting walking or respiratory problems (ie, leg weakness, foot drop, and rapidly ascending sensory changes). Severe may be GBS and should be managed as such. | - Permanently discontinue ICPi.
- Admit patient.
- Neurology consultation.
- Initiate IV methylprednisolone 2 to 4 mg/kg/day and proceed as per GBS management.
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| 7.4. Autonomic neuropathy |
Work-up and evaluation: - An evaluation by neurologist or relevant specialist depending on organ system, with testing that may include:
- Screen for other causes of autonomic dysfunction: diabetic screen, adrenal insufficiency, HIV, paraproteinemia, amyloidosis, and botulism; consider chronic diseases such as Parkinson's and other autoimmune screen.
- Orthostatic vital signs.
- Consider electrodiagnostic studies (NCS and EMG) to evaluate for concurrent polyneuropathy.
- Consider paraneoplastic autoimmune dysautonomia antibody testing (eg, antiganglionic AChR, ANNA-1, and N-type voltage-gated calcium channel antibodies).
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| Grading | Management |
| G1: Mild: no interference with function and symptoms not concerning to patient. | - Low threshold to hold ICPi and monitor symptoms for a week. If to continue, monitor very closely for any symptom progression.
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| G2: Moderate: some interference with ADLs, symptoms concerning to patient. | - Hold ICPi and resume once return to ≤G1 and off prednisone if used.
- Initial observation or initiate prednisone 0.5 to 1 mg/kg/day (if progressing from mild).
- Neurology consultation.
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| G3-4: Severe: limiting self-care and aids warranted. | - Permanently discontinue ICPi.
- Admit patient.
- Initiate methylprednisolone 1 g daily for 3 days followed by oral steroid taper.
- Neurology consultation.
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| 7.5. Aseptic meningitis |
Work-up and evaluation: - MRI brain with or without contrast with pituitary or sellar cuts protocol.
- AM cortisol, ACTH to rule out adrenal insufficiency.
- Strongly consider lumbar puncture with CSF analysis for opening pressure, cell count and differential, cytology for malignant cells that could indicate leptomeningeal metastases, protein, glucose, gram stain, viral or bacterial cultures, PCR for HSV, and other viral PCRs depending on suspicion.
- May see elevated WBC in CSF with normal glucose, normal culture, and gram stain. May see reactive lymphocytes, neutrophils, or histiocytes on cytology.
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| Grading | Management |
G1: Mild: no interference with function and symptoms not concerning to patient. NOTE: any cranial nerve problem should be managed as moderate.
G2: Moderate: some interference with ADLs, symptoms concerning to patient (ie, pain but no weakness or gait limitation).
G3-4: Severe: limiting self-care and aids warranted. | - Hold ICPi and discuss resumption with patient only after taking into account the risks and benefits.
- Consider neurology consult.
- Consider empiric antiviral (IV acyclovir) and antibacterial therapy until CSF results.
- Once bacterial and viral infection negative, may closely monitor off corticosteroids or consider oral prednisone 0.5 to 1 mg/kg/day or IV methylprednisolone 1 mg/kg/day if moderate or severe symptoms.
- Steroids can be tapered after 2 to 4 weeks, monitoring for symptom recurrence.
- Consider hospitalization for G3-4.
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| 7.6. Encephalitis |
Work-up and evaluation: - Neurologic consultation.
- MRI brain with or without contrast may reveal T2/FLAIR changes typical of what is seen in autoimmune encephalopathies or limbic encephalitis or may be normal.
- Lumbar puncture with CSF analysis for opening pressure, cell count and differential, cytology for malignant cells that could indicate leptomeningeal metastases, protein, glucose, gram stain, viral or bacterial cultures, PCR for HSV and other viral PCRs depending on suspicion, oligoclonal bands, autoimmune encephalopathy, and paraneoplastic panels.
- May see elevated WBC with lymphocytic predominance and/or elevated protein.
- EEG to evaluate for subclinical seizures.
- Serum studies: Chem panel, CBC, ESR, CRP, ANCA (if suspect vasculitic process), thyroid panel including TPO and thyroglobulin, AM cortisol and ACTH, GQ1b antibodies (Bickerstaff encephalitis and rhomboencephalitis), celiac antibody panel, and paraneoplastic and autoimmune encephalitis panels.
- Rule out concurrent anemia/thrombocytopenia, which can present with severe headaches and confusion.
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| Grading | Management |
G1: Mild: No interference with function and symptoms not concerning to patient. NOTE: any cranial nerve problem should be managed as moderate.
G2: Moderate: Some interference with ADLs, symptoms concerning to patient (ie, pain but no weakness or gait limitation).
G3-4: Severe: Limiting self-care and aids warranted. | - Hold ICPi and discuss resumption with patient only after taking into account the risks and benefits.
- As above for aseptic meningitis suggest concurrent IV acyclovir until PCR results obtained and negative.
- Trial of methylprednisolone 1 to 2 mg/kg/day.
- Neurology consultation.
- If severe or progressing symptoms or oligoclonal bands present, consider pulse corticosteroids (methylprednisolone 1 g IV daily for 3 to 5 days) plus IVIG 2 g/kg over 5 days (0.4 g/kg/day) or plasmapheresis.
- Taper steroids following acute management over at least 4 to 6 weeks.
- If positive for autoimmune encephalopathy or paraneoplastic antibody or limited or no improvement, consider rituximab in consultation.
- Admit patient for G3-4.
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| 7.7. Demyelinating diseases, including multiple sclerosis, transverse myelitis, ADEM, ON, and NMO |
Work-up and evaluation: - Neurologic consultation.
- Ophthalmic or neuro-ophthalmic evaluation if ocular involvement.
- MRI with contrast of brain, orbit, cervical, and thoracic spinal cord (tailor to examination finding).
- Lumbar puncture with CSF analysis including autoimmune encephalitis panel and oligoclonal bands, CNS demyelinating disease antibodies (aquaporin 4 and myelin oligodendrocyte glycoprotein), and viral PCRs especially JCV PCR to exclude progressive multifocal leukoencephalopathy.
- Serum studies: B12, HIV, RPR, ANA, Ro/La, TSH, aquaporin-4 IgG, paraneoplastic panel or anti-HU and anti–CRMP5-CV2, thyroid panel including TPO and thyroglobulin, AM cortisol and ACTH, and paraneoplastic and autoimmune encephalitis panels.
- Evaluation for urinary retention and constipation.
- EEG to evaluate for subclinical seizures.
- Although less common, biopsy may provide definitive evidence of CNS demyelination.
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| Grading | Management |
| G1: Asymptomatic or mild symptoms; clinical or diagnostic observations only. | - Intervention not indicated.
- Continue immunotherapy unless symptoms worsen or do not improve.
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| G2: Moderate symptoms; minimal, limiting age-appropriate instrumental ADL. | - Stop ICPi.
- Neurology consultation.
- Start prednisone 1 mg/kg daily and taper over 1 month.
- Rule out infection.
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| G3: Severe or medically significant symptoms but not immediately life-threatening; limiting self-care ADL. | - Permanently discontinue ICPi.
- Neurology consultation.
- Nonopioid management of neuropathic pain, for example, pregabalin, gabapentin, or duloxetine.
- Admit patient for methylprednisolone pulse dosing 1 g/day and consider IVIGΔ or plasmapheresis if no improvement or symptoms worsen after 3 days.◊
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| G4: Life-threatening consequences. | - Permanently discontinue ICPi.
- Neurology consultation.
- ICU level inpatient care.
- Start methylprednisolone pulse dosing 1 g/day and consider IVIG or plasmapheresis if no improvement or symptoms worsen after 3 days.◊
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