Transverse Myelitis - Comprehensive Notes

Definition

• Incidence: approximately 1 in 100,000 people (rare)
• Commonly monophasic, though recurrent forms exist

Etiology & Classification

• No identifiable cause found

• Follows viral infection in ~30% of cases
• Causative organisms: HSV, VZV, CMV, EBV, enterovirus, rabies
• Also postexanthematous (measles, rubella) and postvaccinal (rabies, polio vaccines)

• Multiple sclerosis (MS) - typically incomplete/partial TM
• Neuromyelitis optica spectrum disorder (NMOSD) - associated with anti-AQP4 IgG
• MOG antibody disease (MOGAD)
• Systemic lupus erythematosus (SLE)
• Sjögren syndrome
• Antiphospholipid antibody syndrome
• Mixed connective tissue disease
• Vasculitis
• Sarcoidosis
• Paraneoplastic myelopathy

• Spinal cord ischemia / infarction
• Dural arteriovenous fistula
• Antiphospholipid syndrome

• Disc herniation, spondylosis, trauma
• Spinal epidural abscess (SEA)
• Spinal epidural hematoma (SEH)
• Primary or metastatic spinal neoplasm

Pathophysiology

• Presumed autoimmune mechanism with inflammatory infiltration of the cord
• Anti-AQP4 antibodies (aquaporin-4 water channel) implicated in NMOSD-associated TM
• Demyelination and variable axonal injury lead to conduction block
• The thoracic cord is involved in 60-70% of cases; cervical cord is rarely affected
• Complete lesions destroy the entire cord cross-section; incomplete lesions spare some tracts

Clinical Features

Classic Triad

1. Motor deficits - paraparesis or paraplegia below the lesion level
2. Sensory level - loss of all modalities (especially pin-prick/temperature) below a distinct dermatomal level
3. Sphincter/autonomic dysfunction - bladder, bowel, and sexual dysfunction

Detailed Features (by system)

• Acute phase: flaccid paralysis (spinal shock) - absent reflexes
• Subacute/chronic: spastic paraplegia - hypertonia, hyperreflexia, clonus, bilateral Babinski signs
• Loss of superficial abdominal and cremasteric reflexes
• Paraplegia (incomplete = more common in MS) vs. complete paraplegia (more common in idiopathic TM/NMOSD)

• Ascending paresthesias
• Distinct sensory level on the trunk (most valuable localizing sign)
• Loss of deep sensibility (vibration, proprioception) in the feet
• Band-like radicular pain or segmental paresthesias at the lesion level
• Note: sensory level may be several segments below actual lesion with extramedullary lesions

• Bladder dysfunction (retention, incontinence)
• Bowel dysfunction (constipation, incontinence)
• Sexual dysfunction
• With cervical/high thoracic lesions: hypo- or hypertension, brady- or tachycardia

• Back pain (localized to lesion level)
• Low-grade fever
• Onset: rapid progression - 66% reach maximal deficit within 24 hours; some progress over days to weeks

Longitudinally Extensive TM (LETM)

• Lesion spanning 3 or more vertebral body levels (rostrocaudal)
• Hallmark of NMOSD (neuromyelitis optica spectrum disorder)
• Should prompt testing for anti-AQP4 antibodies
• Associated with worse prognosis than limited/partial TM

Investigations

MRI (Gold Standard)

• Modality of choice - MRI spine with gadolinium
• Findings:
  • T2 hyperintense signal within the cord
  • Cord swelling/enlargement
  • Gadolinium enhancement (active inflammation)
• LETM: signal spanning ≥3 vertebral segments
• MS-associated TM: short lesion (<2 vertebral segments), peripheral/asymmetrical
• Brain MRI: essential to look for demyelinating lesions suggesting MS

CSF Analysis

• Normal in 40% of cases
• Abnormal (remaining 60%): mild lymphocytic pleocytosis + mildly elevated protein
• Oligoclonal bands suggest MS
• Elevated IgG index

Serology

• Anti-AQP4 (NMO-IgG): positive in NMOSD - diagnostic
• Anti-MOG antibodies: MOG antibody disease
• ANA, anti-dsDNA: SLE
• Antiphospholipid antibodies (aPL, lupus anticoagulant)
• SSA/SSB antibodies: Sjögren syndrome

Spinal Angiography

• Indicated in: older patients, vascular risk factors, or central cord edema pattern on MRI
• To exclude spinal cord ischemia or dural AV fistula

Differential Diagnosis

Treatment

Acute/Initial

• Methylprednisolone 1000 mg IV daily for 3-5 days - standard first-line treatment
• Aimed at reducing inflammation and shortening attack duration
• Note: limited RCT evidence, but widely used in clinical practice

Steroid-Refractory Cases

• Plasma exchange (PLEX) - 5-7 exchanges over 10-14 days
• IVIG (intravenous immunoglobulin)
• Cyclophosphamide - for severe or refractory cases

NMOSD-Specific Long-Term Prophylaxis (relapse prevention)

• Satralizumab (anti-IL-6 receptor monoclonal antibody): 120 mg SC at 0, 2, 4 weeks, then every 4 weeks
• Eculizumab (terminal complement inhibitor): 900 mg IV weekly x4, then 1200 mg every 2 weeks
• Tocilizumab (IL-6 receptor inhibitor): 8 mg/kg IV every 4 weeks
• Rituximab: 1000 mg IV x2 (2 weeks apart), every 6 months
• Azathioprine: 3 mg/kg/day

Supportive Management

• Hospitalization usually required
• Neurological consultation
• Bladder care (catheterization)
• DVT prophylaxis
• Physiotherapy, occupational therapy
• Neuropathic pain management
• Bowel management

Prognosis

• Recovery typically begins within 1-3 months after onset
• Maximal improvement reached by 3-6 months
• Overall significant recovery in fewer than 50% of patients
• Many patients with severe disease remain completely paralyzed after the initial attack
• Prognosis is worse than in MS for individual attacks
• Fewer than half of patients develop MS or clinical dissemination within 5 years of an isolated myelitis attack

Favorable Prognostic Factors

• Early treatment
• Partial/incomplete lesion
• Younger age
• Rapid onset (paradoxically may indicate better recovery than gradual onset)

Unfavorable Prognostic Factors

• Complete cord lesion
• NMOSD association
• LETM
• Rapid progression to maximal deficit

Relationship to MS and NMOSD

MS vs. Idiopathic TM

• In MS: TM is typically partial and asymmetric (not truly "transverse")
• Lesion is short (<2 segments), peripheral location in cord
• Brain MRI shows periventricular/Dawson finger plaques
• Risk of developing clinically definite MS after isolated myelitis: ~1/3 within 5 years

NMOSD

• Characterized by fulminant LETM + optic neuritis (often bilateral)
• Anti-AQP4 IgG is diagnostic; seronegative NMOSD also recognized
• Brain MRI lesions may be present, with predilection for brainstem
• High risk of relapse and disability if not treated with long-term immunosuppression

MOG Antibody Disease (MOGAD)

• Distinct from both MS and NMOSD
• Anti-MOG antibodies
• May present with TM (often LETM), optic neuritis, or ADEM
• Generally monophasic; better prognosis than NMOSD

Key Points Summary

1. TM = bilateral motor + sensory level + sphincter dysfunction, acute/subacute onset
2. Thoracic cord most common (60-70%)
3. LETM (≥3 levels) = think NMOSD, test for anti-AQP4
4. MRI with gadolinium is the investigation of choice
5. CSF is normal in 40% - normal CSF does not exclude TM
6. First-line treatment: IV methylprednisolone 1g/day x 3-5 days
7. Refractory cases: plasma exchange, IVIG, cyclophosphamide
8. Prognosis varies - good recovery in only ~30%; complete paralysis persists in many
9. Always distinguish from compressive/structural causes (require urgent surgery)
10. Long-term NMOSD prophylaxis with biologics (eculizumab, satralizumab, tocilizumab) significantly reduces relapse risk

Hydrocephalus - Comprehensive Notes

Definition

• Total normal CSF volume: ~150 mL
• CSF production rate: ~20 mL/hour (~500 mL/day)
• Most cases result from impaired flow or resorption - overproduction is rare

CSF Physiology (Normal Pathway)

1. Production: Choroid plexuses of the lateral, third, and fourth ventricles (also produced from the walls of the ventricles)
2. Flow path: Lateral ventricles → Foramen of Monro → Third ventricle → Cerebral aqueduct (of Sylvius) → Fourth ventricle → Exit via:
   • Foramen of Magendie (midline, posterior)
   • Foramina of Luschka (lateral, ×2)
3. Circulation: Into the subarachnoid space, bathing the brain and spinal cord
4. Absorption: Primarily via arachnoid granulations (arachnoid villi) along the superior sagittal sinus; also via brain and cord lymphatics
5. Cerebrovascular pulsations influence the net flow through the ventricular system

Classification

1. Obstructive (Non-Communicating) Hydrocephalus

• Obstruction within the ventricular system - CSF cannot reach the subarachnoid space
• Ventricles proximal to the obstruction dilate; distal ones do not
• Most common site: cerebral aqueduct (aqueductal stenosis)
• LP is contraindicated (risk of herniation/"coning" due to differential pressure)

2. Communicating Hydrocephalus

• Ventricular system remains in continuity with the subarachnoid space
• Obstruction at the level of arachnoid granulations or impaired absorption
• Entire ventricular system is enlarged
• LP is diagnostic and therapeutic (can drain 10-30 mL for temporary relief)

3. Hydrocephalus Ex Vacuo

• Not true hydrocephalus
• Compensatory ventricular enlargement secondary to loss of brain parenchyma (atrophy)
• No elevated ICP; no treatment required
• Seen in Alzheimer disease, cerebrovascular disease

4. Overproduction Hydrocephalus (Rare)

• Due to choroid plexus papilloma/carcinoma
• May also cause obstructive hydrocephalus via mass effect or haemorrhage

Etiology

Obstructive Causes

Communicating Causes

• Post-haemorrhagic (subarachnoid haemorrhage, intraventricular haemorrhage)
• Post-infective meningitis (arachnoid fibrosis)
• Raised CSF protein (spinal cord tumours, Guillain-Barré)
• Venous hypertension (craniosynostosis, dural venous sinus thrombosis, vascular malformations)
• Leptomeningeal carcinomatosis
• Idiopathic (NPH)

Congenital Causes

• Aqueductal stenosis/gliosis
• Chiari II malformation (with myelomeningocele)
• Dandy-Walker malformation (absent/hypoplastic vermis + enlarged posterior fossa cyst)
• Vein of Galen malformation
• Congenital midline tumours
• In utero infection causing aqueductal scarring

Pathophysiology

• Increased CSF volume → ventricular expansion → elevated ICP
• Acute hydrocephalus: reaches 80% of maximal ventricular enlargement within 6 hours
• Continued CSF production despite obstruction → fluid accumulates in periventricular white matter → interstitial (transependymal) oedema
• Chronic phase: CSF pressure may normalize - "compensated" state
• Long-term monitoring reveals intermittent nocturnal ICP spikes even when daytime pressure appears normal
• Compression of adjacent structures:
  • Corticospinal tracts (leg spasticity)
  • Optic pathways (papilloedema, visual loss)
  • Brainstem (in severe/acute cases)

Clinical Features

Infants (before 2 years - sutures open)

Older Children (sutures fused)

• Early morning headache (worse on waking, coughing, bending)
• Nausea and vomiting (particularly projectile)
• Papilloedema (risk of secondary optic atrophy and visual loss)
• Altered conscious level
• Leg spasticity, cranial nerve palsies
• Head enlargement and fontanelle signs absent (sutures fused)
• Most common causes: posterior fossa neoplasms, aqueductal stenosis

Adults

• Raised ICP symptoms: headache (worse in morning/lying down), vomiting, papilloedema
• Visual obscurations, diplopia (CN VI palsy)
• Altered consciousness, coma (if acute/severe)
• Acute life-threatening hydrocephalus: cerebellar infarct/hemorrhage blocking 4th ventricle outflow → rapid deterioration

Normal Pressure Hydrocephalus (NPH)

Definition

• Chronic communicating adult-onset hydrocephalus with enlarged ventricles but normal CSF pressure on LP (150-200 mm H2O)
• First described by Adams, Fisher, and Hakim
• Prevalence: ~0.2% in 70-79 year olds, ~5.9% in those over 80

Classic Hakim-Adams Triad ("wet, wacky, wobbly")

1. Gait disturbance - earliest and most prominent feature
2. Cognitive impairment - subcortical dementia
3. Urinary incontinence - appears latest

Gait Characteristics (NPH gait)

• Apraxic/magnetic gait - feet appear "glued to the floor"
• Short step length, wide base, slow cadence
• Unsteadiness and impaired balance
• Greatest difficulty on stairs and curbs
• No true tremor, rigidity, or festination (distinguishing from Parkinson disease)
• May mimic Parkinsonism superficially
• Progressive: eventually standing and sitting become impossible

Cognitive Features (subcortical dementia)

• Slowing of verbal and motor responses ("psychomotor slowing")
• Apathy and apparent depression
• Preservation of cortical functions (language, spatial ability) early on
• Memory impairment develops later
• Grasp reflexes (feet); no Babinski signs typically
• No papilloedema; headache uncommon

Urinary Features (appears late)

• Urgency → urge incontinence → "frontal lobe incontinence" (indifference to incontinence)
• Eventually bowel incontinence in advanced cases

Etiology of NPH

• Idiopathic: ~1/3 of cases (possibly silent fibrosing meningitis, decompensated congenital aqueductal stenosis)
• Secondary (~2/3): subarachnoid haemorrhage, meningitis (tubercular, fungal, syphilitic), head trauma, Paget disease of skull, mucopolysaccharidoses

Why "Normal Pressure" is a Misnomer

• Long-term monitoring shows intermittent nocturnal ICP spikes
• CSF pressure was likely elevated initially when ventricular enlargement began
• Once equilibrium between production and absorption is reached, daytime pressure normalizes

Investigations

Imaging

• Initial investigation of choice in acute setting
• Shows dilated ventricles ± transependymal oedema (periventricular hypodensity)
• Identifies aqueductal obstruction, posterior fossa masses
• Serial scans to monitor progression
• NPH: dilated ventricles with relatively preserved cortical sulci (ventricular-sulcal disproportion)

• Superior soft tissue detail
• T2/FLAIR: transependymal periventricular hyperintensity (oedema)
• Phase-contrast MRI: can visualize CSF flow at the aqueduct
• Evaluates underlying cause (tumour, Chiari, aqueductal stenosis)
• NPH: Evans' ratio (maximal frontal horn width / inner skull diameter) > 0.3; acute callosal angle < 90°
• Aquagraph MRI: detects rapid flow void at aqueduct ("jet sign") suggesting aqueductal stenosis

• Disproportionate ventricular enlargement vs. sulcal atrophy
• Temporal horn enlargement
• Periventricular transependymal CSF signal
• Contrast to Alzheimer disease (hydrocephalus ex vacuo): both sulci and ventricles enlarged proportionately

CSF Studies (LP)

• Contraindicated in obstructive (non-communicating) hydrocephalus - risk of herniation
• In communicating hydrocephalus / NPH:
  • Opening pressure: usually normal (~150-200 mm H2O) in NPH
  • CSF contents: sent for protein, glucose, cells, cultures, cytology
  • Large-volume tap test: removal of 20-40 mL CSF; gait improvement = positive test → predicts shunt response
  • Continuous lumbar drainage (3-5 days) improves diagnostic accuracy for shunt response

Radionuclide Cisternography

• Intrathecal injection of radiolabelled tracer
• Normally: tracer flows over cerebral convexities by 24 hours
• NPH pattern: reflux of tracer into ventricles, delayed clearance from basal cisterns
• Not used routinely, but may help in selected cases

External Ventricular Drain (EVD)

• Both diagnostic and therapeutic
• Measures ICP directly; allows controlled CSF drainage
• Used in acute hydrocephalus

Treatment

Acute / Emergency

• External ventricular drain (EVD): first-line for acute obstructive hydrocephalus - removes CSF and directly monitors ICP
• Manage underlying cause urgently
• For posterior fossa masses: urgent neurosurgical decompression

Surgical (Definitive)

• Catheter from lateral ventricle → programmable valve → peritoneal cavity
• Treatment of choice for communicating hydrocephalus and NPH
• Complications: blockage (by choroid plexus or glial tissue), infection (1-5%), overdrainage, shunt fracture/disconnection

• Catheter to right atrium
• Used when peritoneal route not feasible
• Complications: cardiac arrhythmia, septicaemia, pulmonary hypertension

• Surgical perforation of the floor of the third ventricle → CSF drains into suprasellar cistern
• Ideal for: aqueductal stenosis, obstructive hydrocephalus
• Avoids implanted hardware → no shunt infection risk
• Patency confirmed by T2 MRI: large hypointense flow void through the ventriculostomy
• Contraindicated in communicating hydrocephalus

• Lumbar subarachnoid space → peritoneal cavity
• Used for NPH and communicating hydrocephalus

Medical / Temporary

• Acetazolamide + furosemide: reduce CSF production (used in premature infants with posthemorrhagic hydrocephalus while awaiting surgery, and in IIH)
• Repeated LP drainage: temporary in communicating hydrocephalus

Shunt Complications & Assessment

• Shunt obstruction: most common complication; recurrence of symptoms + ventricular dilatation on imaging
• Shunt infection (ventriculitis): incidence 1-5%; features include fever, meningism, and CSF pleocytosis; ependymal enhancement on MRI
• Overdrainage: slit ventricle syndrome, subdural hygroma/hematoma
• Plain skull X-ray + abdominal X-ray (shunt series): assess integrity of tubing, disconnection, calcification
• CT head: compare ventricular size to baseline

NPH - Shunt Selection Algorithm

1. Clinical triad present → FLAIR MRI brain
2. Communicating hydrocephalus on MRI (without excessive cortical atrophy, with transependymal absorption) → Large-volume LP (20-40 mL)
3. Gait improvement post-LP → VP shunt placement
4. White matter changes / lacunar disease → Likely vascular dementia/parkinsonism, poor shunt response
5. Coexisting Parkinson disease → Rule out hydrocephalus; shunt response unpredictable

• Gait disturbance as the predominant and earliest feature
• Short duration of symptoms
• Identifiable secondary cause (e.g. SAH)
• Minimal cortical atrophy on imaging
• Clear improvement on tap test

• Prominent cognitive/language impairment preceding gait disorder
• Extensive white matter changes (Binswanger disease, lacunar infarcts)
• Severe cortical atrophy

Dandy-Walker Malformation

• Triad: (1) hypoplasia/aplasia of the cerebellar vermis, (2) cystic dilation of the fourth ventricle, (3) enlarged posterior fossa
• Associated with aqueductal obstruction → hydrocephalus
• Treatment: VP shunt or cyst fenestration

Key Differentials

Key Points Summary

1. Hydrocephalus = increased CSF in ventricles - from obstruction, impaired absorption, or (rarely) overproduction
2. Non-communicating = intraventricular obstruction (aqueductal stenosis most common); LP contraindicated
3. Communicating = extraventricular; LP is diagnostic and can be therapeutic
4. CSF path: Lateral ventricles → Foramen of Monro → 3rd ventricle → Aqueduct of Sylvius → 4th ventricle → Foramina of Magendie & Luschka → subarachnoid space → arachnoid granulations
5. Infants: macrocephaly, bulging fontanelle, sunsetting eyes; Adults: headache, vomiting, papilloedema; NPH: gait + cognition + incontinence
6. MRI is the gold standard imaging modality; Evans' ratio >0.3 supports NPH
7. Acute management: external ventricular drain
8. Definitive treatment: VP shunt (most common) or endoscopic third ventriculostomy (ETV)
9. NPH tap test: LP removal of 20-40 mL + gait improvement → proceed to VP shunt
10. Shunt complications: obstruction (most common), infection (1-5%), overdrainage