White Matter Disease Neurology Rotation Lecture Series Last Updated by Lindsay Pagano Summer 2013

Case Presentation The ED calls you in consultation for a 10 year old female with fever, altered mental status and weakness. Normal state of health until 7 days ago when she developed cough and fever In the last 2 days, started acting irritable and then sleepy Over the last 24 hours, has developed right sided weakness General exam: crackles on lung exam Neuro exam: pertinent positives –MS: sleepy but arousable with slightly painful stimulation –Motor: right UE and LE with 1-2/5 strength diffusely, hypotonia –Reflexes: brisk on the right –Sensory: responds to painful stimulation in all 4 extremities Differential?

ADEM Acute disseminated encephalomyelitis Presents with –Altered mental status/encephalopathy (irritability to obtunded) –Acute/subacute onset of focal symptoms based on lesions (max neuro symptoms over 4-7 days) –Typically still during febrile illness (typically URI) –1/3 with seizures Workup –Labs: none are diagnostic –CSF: pleocytosis, elevated protein, elevated IgG index; rule out infection! –Imaging: MRIbrain with contrast Treatment: IV steroids (ok to start while r/o infection and prophylactic antibiotics are on board) > IVIg > PLEX; PT Outcome –Recovery over 4-6 weeks % with no residual defecits –Repeat MRI 6-12 months later to assess for lesion resolution

Guillain-Barré Syndrome Aka AIDP, acute inflammatory demyelinating polyneuropathy History: febrile illness 2-4 weeks prior to onset pain, paresthesias and ascending weakness Pathophysiology –grouping of acute immune mediated polyneuropathies (cross reacting Ab to GM1 ganglioside) – both humoral factors and cell-mediated immune phenomena that damage myelin and/or the myelin-producing Schwann cells –2/3 with antecedent respiratory or diarrheal illness 2-4 weeks prior; c. jejuni most frequent (30%) Neuro Exam: distal > proximal weakness, hypotonia and areflexia; sensation testing may be intact despite subjective feelings of numbness and paresthesias Be wary of potential autonomic involvement! Monitor on tele, q4h nifs, continuous pulse ox Workup –Labs: None –LP: albuminocytologic dissociation –EMG/NCV: demyelination (  slowed nerve conduction velocities) –MRI: not indicated for diagnosis (MRIspine would show nerve root enhancement) Treatment: IVIg > PLEX + PT –Treatment doesn’t change overall outcome/degree of recovery Recovery over weeks-couple months; initial severity doesn’t correlate with length of course

Transverse Myelitis Focal inflammatory disease process of the spinal cord –Affects motor, sensory and autonomic fibers –Up to 50% with preceding febrile illness Highest incidence between yo, yo (bimodal) Present with –Acute/subacute onset of pain, weakness, sensory loss, incontinence over hours-weeks –80% of cases are in the thoracic spine Neuro exam: depends on where the lesion is! –Typically bilateral weakness with UMN signs, but… –If anterior horn cells are involved, may get a predominantly LMN exam Workup: –Labs: none positive for this condition, but can get labs to rule out other disease processes –CSF: pleocytosis, elevated IgG index –Imaging: MRIspine, with and without contrast Treatment: IV steroids + PT Outcome: 1/3 no long term sequelae, 1/3 mild-moderate disability, 1/3 severe disability

Multiple Sclerosis Chronic demyelinating disease 5% patients present before age 18 –95% of these have a relapsing remitting course: little to no disability inbetween flares (versus primary progressive, secondary progressive, progressive relapsing) MacDonald Criteria for diagnosis: lesions separated by space and time –Check the FLAIR and post contrast to help date lesions in 1 st presentation Presentation/Neuro exam: dependent on location of lesions –No prodromal illness –Not all lesions are symptomatic Workup –Labs: none diagnostic –CSF: pleocytosis, increased protein, elevated IgG index/oligoclonal bands present –Imaging: MRIbrain with contrast Periventricular lesions Dawson’s fingers –Visual evoked potentials (slowed conduction if optic nerves affected) Treatment –Acute: MS trial: IV methyprednisolone + steroid taper –Long term: interferon, glatiramir

Neuromyelitis Optica Aka NMO, Devic Disease Diagnostic Criteria 1. Optic neuritis AND 2. Transverse myelitis AND 3. -MRI evidence of myelitis incolving 3 or more contiguous segments OR -NMO-IgG + (aquaporin 4, found in serum) The above do not have to occur simultaneously May also have CNS lesions and resulting symptoms Clinical course is primary progressive or relapsing-remitting Worse recovery of vision [from optic neuritis] and strength [from myelopathy] as compared to MS 93% with recurrent attacks, 90% with residual disability

PREP question A 12 year old girl presents with a 2 day history of progressive back pain and difficulty walking, especially up stairs. This morning she had trouble dressing and combing her hair. On PE, the girls vital signs and stable and she is not short of breath. Cardiac, pulmonary, and joint evaluation results are normal. Neurologic exam reveals normal mental status and cranial nerves. Strength is diffusely reduced in the arms and legs, and reflexes are absent. Her gait is slow, and she requires assistance Ato arise from the floor. Noncontrast head CT scan results are normal. Forced vital capacity is normal. LP reveals a CSF protein of 100 mg/dL. CSF WBC count, RBC count and glucose are normal. You admit the girl for cardiorespiratory monitoring and treatment. Of the following, the treatment that is MOST likely to be beneficial in hastening this child’s recovery is: A.Immune globulin intravenously B.Methotrexate intrathecally C.Methylprednisolone intravenously D.Neostigmine intravenously E.Tissue plasminogen activator intravenously

A. IVIg GBS (Guillain-Barre syndrome) aka AIDP (acute inflammatory demyelinating polyneuropathy) –Localize! –Albuminocytologic dissociation –IVIg 2g/kg divided over 3 vs 5 days (may pretx) –Need to monitor respiratory (NIFs, FVCs) and cardiovascular (tele) status, ICU if needed Regarding the other choices: B. Methotrexate IV: chemotherapy used for CNS malignancy C. Methyprednisolone IV: not effective as monotherapy D. Neostigmine IV: acetylcholinesterase inhibitor, for NMJ junction disease, eg myasthenia gravis E. tPA IV: given in adult acute stroke