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Causes of Acute Paraparesis

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Localizing the Level First

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I. Spinal Cord Causes (Most Common)

A. Compressive / Extrinsic

B. Intrinsic / Noncompressive — Vascular

C. Intrinsic / Noncompressive — Inflammatory / Demyelinating

D. Intrinsic / Noncompressive — Infectious

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II. Cauda Equina / Conus Medullaris

• Massive midline lumbar disc prolapse — most common; acute back pain + bilateral leg weakness + urinary retention
• Cauda equina tumor (ependymoma, schwannoma, meningioma)
• Lumbosacral trauma
• HIV-related acute lumbosacral polyradiculopathy (CMV in immunocompromised)
• Spinal epidural abscess/hematoma at lumbar level

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III. Cerebral / Supratentorial Causes (Rare)

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IV. Peripheral / Neuromuscular Causes

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Approach Summary

Acute paraparesis
     ├── Sensory level / UMN signs → Spinal cord MRI STAT
     │        ├── Compressive? → Surgery/Antibiotics emergency
     │        └── Noncompressive? → LP + autoimmune/infectious workup
     ├── No sensory level, flaccid/areflexic → Cauda equina vs. GBS vs. myopathy
     └── Bilateral leg UMN + brain signs → Brain MRI (ACA infarct, SST)

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Approach to a 55-Year-Old with 2 Episodes of Seizures + Altered Sensorium

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Step 1 — Initial Stabilization (Before History)

• Airway, breathing, circulation
• Capillary blood glucose immediately (hypoglycemia is the most treatable cause)
• IV access, pulse oximetry, cardiac monitor
• GCS score
• Is the patient still seizing? → If so, manage as status epilepticus

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Step 2 — HISTORY

A. Confirm It Was a Seizure (Not a Mimic)

• Onset: sudden or gradual?
• Type of movements: tonic? clonic? tonic-clonic? focal limb jerking? head/eye deviation?
• Duration of episode (exact)
• Was there a cry/vocalization at onset?
• Did the patient fall? Sustain injury?
• Skin color: cyanosis, pallor?
• Loss of consciousness: complete or partial?
• Tongue biting (lateral tongue bite → seizure; tip bite → syncope)
• Incontinence (urinary/fecal)
• Post-episode behavior: confusion, drowsiness, Todd's paralysis, headache, amnesia?

• Syncope (preceded by prodrome — nausea, diaphoresis, pallor; recovery rapid)
• Cardiac arrhythmia (ventricular tachycardia; palpitations; ECG abnormality)
• TIA (loss of function, not spreading excitation; no post-ictal confusion)
• Hypoglycemic episode
• Psychogenic non-epileptic seizures (PNES)
• Migraine with aura

B. Characterize the Seizure Type

• Focal onset (aware or impaired awareness) vs. generalized → critical for workup
• Any aura beforehand? Olfactory, gustatory, déjà vu, rising epigastric feeling → temporal lobe
• Visual/sensory aura → occipital/parietal
• Second episode — same or different semiology? What interval?
• Did patient have eye/head deviation at onset? → indicates contralateral frontal focus

C. History of Present Illness

• Fever, headache, neck stiffness, photophobia → meningoencephalitis (urgent)
• Headache (progressive, worse lying flat) → raised ICP, SOL
• Focal weakness, speech disturbance, vision change → structural lesion
• Vomiting → raised ICP
• Recent head trauma (even trivial) → subdural/extradural hematoma
• Altered behavior/personality change over weeks → tumor, encephalitis (autoimmune/viral)
• Fever + rash → HSV encephalitis, bacterial meningitis, CNS vasculitis
• Polyuria, polydipsia → hypo-/hyperglycemia, hyponatremia
• Recent illness / vaccination → ADEM
• Recent travel → neurocysticercosis (endemic areas), cerebral malaria, TB
• Timeline of altered sensorium relative to seizures

D. Past Medical History

E. Drug and Substance History

F. Family and Social History

• Family history of epilepsy
• Occupation (driver? — implications for treatment)
• Lives alone?
• Sleep deprivation, extreme physical or emotional stress

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Step 3 — EXAMINATION

General Examination

Neurological Examination (Systematic)

1. Level of Consciousness & Cognition

• GCS (E+V+M) — document precisely
• MMSE / orientation — time, place, person
• Is this true postictal drowsiness or new encephalopathy?
• Postictal state: usually improves steadily over 20–60 min; persisting confusion → structural/metabolic

2. Meningeal Signs

• Neck stiffness (Kernig's sign, Brudzinski's sign) → meningitis, SAH, encephalitis
• Note: may be absent in immunocompromised / elderly

3. Cranial Nerves

4. Motor System

• Focal weakness → contralateral structural lesion
• Todd's paralysis — transient hemiparesis after focal seizure (30 min – 36 h); clears spontaneously
• Tone: hypotonia (metabolic/toxic), spasticity (structural)
• Pronator drift
• Plantar response (upgoing Babinski → UMN lesion or postictal)

5. Sensory System

• Hemisensory loss → contralateral parietal lesion

6. Cerebellar

• Ataxia, nystagmus → posterior fossa lesion, drug toxicity (phenytoin, carbamazepine)

7. Deep Tendon Reflexes

• Hyperreflexia + Babinski → UMN lesion
• Hyporeflexia → metabolic, drug effect

8. Fundoscopy (MANDATORY)

• Papilloedema → raised ICP → LP contraindicated before imaging

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Differential Diagnosis Framework (55-Year-Old)

Seizures + Altered Sensorium at 55 yrs
│
├── STRUCTURAL (most common in this age)
│    ├── Stroke (ischemic / hemorrhagic)
│    ├── Subdural / extradural hematoma
│    ├── Brain tumor (primary glioma or metastasis)
│    └── Brain abscess / granuloma (TB, NCC)
│
├── METABOLIC / SYSTEMIC
│    ├── Hypo/hyperglycemia
│    ├── Hyponatremia (Na⁺ <125 mEq/L)
│    ├── Uremic encephalopathy
│    ├── Hepatic encephalopathy
│    ├── Hypocalcemia / hypomagnesemia
│    ├── Hypoxia / hypercapnia
│    └── Hypertensive encephalopathy / PRES
│
├── INFECTIVE / INFLAMMATORY
│    ├── Bacterial meningitis
│    ├── Viral encephalitis (HSV most important)
│    ├── Autoimmune encephalitis (anti-NMDAR, LGI1, CASPR2)
│    ├── TB meningoencephalitis
│    └── Cerebral malaria / neurocysticercosis
│
├── TOXIC / DRUG
│    ├── Alcohol withdrawal (48–72 h after last drink)
│    ├── Benzodiazepine/barbiturate withdrawal
│    └── Drug toxicity (proconvulsants)
│
└── VASCULAR
     └── Cerebral venous sinus thrombosis (CVST)

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Red Flags Demanding Immediate Action

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25-Year-Old Female: Left Hand Wasting + Pure Motor Weakness (3 months, No Sensory Loss)

Key Diagnostic Features to Lock In

• Young female, 25 years
• Unilateral (left hand)
• Wasting + weakness (lower motor neuron pattern — flaccid, ± fasciculations, ± hyporeflexia)
• 3 months — subacute/chronic, not acute
• No sensory loss — this is the critical differentiating feature

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Localization First

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Differential Diagnosis (Most Likely to Least in This Patient)

1. Hirayama Disease (Benign Monomelic Amyotrophy / Juvenile Segmental Muscular Atrophy) ⭐ TOP DIAGNOSIS

"The most common presentation is one of an idiopathic, slowly progressive, painless weakness and atrophy in one hand or forearm... The condition remains limited to only a few myotomes." — Bradley and Daroff's Neurology

• Classic age of onset: teens to early 30s
• More common in women in Indian subcontinent (though 60% are male overall)
• Predominantly C7–T1 myotomes → intrinsic hand muscles + forearm
• "Oblique atrophy" pattern — thenar, hypothenar, interossei wasted; brachioradialis spared
• Pure LMN, no sensory loss, no UMN signs, no cranial nerve involvement
• Painless, slow progression over 2–3 years then stabilizes
• Proposed mechanism: dynamic cord compression during neck flexion (disproportionate dural sac growth)
• EMG: active and chronic denervation at C7–T1; NCS show reduced CMAPs, near-normal SNAPs
• MRI cervical spine (dynamic — flexion views): flattening of anterior cord, loss of attachment of posterior dura, asymmetric cord atrophy

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2. Cervical Myelopathy — Syringomyelia

"Syringomyelia... damage to the fibers crossing in the anterior commissure destined for the spinothalamic tract... By the time descending tracts are affected, segmental motoneuron and corticospinal tract damage are almost always present." — Bradley and Daroff's

• Syrinx classically causes cape-like dissociated sensory loss (pain/temp lost, proprioception preserved)
• However, early syrinx can present with pure hand wasting (anterior horn cell damage at the level of the syrinx) before sensory fibres are involved
• Associated with Chiari malformation (Type I most common), trauma, tumors, arachnoiditis
• May later develop UMN signs in legs (descending tract involvement)
• 25-year-old female + no sensory involvement yet → must exclude with MRI
• MRI spine: T2 fluid-filled cavity within cord over multiple segments

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3. True Neurogenic Thoracic Outlet Syndrome (TOS)

"True neurogenic TOS... compression of the lower trunk (C8/T1)... weakness and wasting of intrinsic muscles of the hand and diminished sensation on the palmar aspect of the fifth digit." — Harrison's Principles

• Caused by anomalous fibrocartilaginous band from elongated C7 transverse process (cervical rib) to first rib
• C8/T1 compression → hand intrinsic wasting
• Pain is mild or absent — can initially appear as pure motor
• Sensory loss on 5th digit/medial forearm — may be minimal or absent early
• Young women, often exacerbated by arm position
• CXR: elongated C7 transverse process / cervical rib
• EMG/NCS: reduced SNAP medial forearm, low CMAP ulnar > median
• Treatment: surgical band resection (wasting usually does not recover but progression halts)

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4. Multifocal Motor Neuropathy (MMN) with Conduction Block

"Pure LMN involvement... enters the differential diagnosis of benign focal amyotrophy and the PMA variant of ALS. It is important to search for this since it is treatable." — Bradley and Daroff's

• Autoimmune; anti-GM1 antibodies in ~50%
• Asymmetric, pure motor — starts distally, upper > lower limbs
• No sensory loss (distinguishes from CIDP)
• Fasciculations may be present
• Can begin with focal hand wasting in a young adult
• EMG/NCS: focal conduction block outside carpal tunnel → pathognomonic
• Treatable — high-dose IVIG; this makes the diagnosis essential to establish
• CK mildly elevated; anti-GM1 IgM elevated

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5. Compressive Focal Motor Neuropathy

• Relevant in occupational/repetitive trauma
• EMG/NCS confirms level and type

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6. Cervical Radiculopathy — C8/T1 Root (Predominantly Motor)

• Disc prolapse or osteophyte compressing C8 or T1 motor root
• Can produce hand intrinsic weakness and wasting
• Sensory involvement is typical but can be minimal or overlooked
• C8: ring/little finger, medial forearm sensory if affected; intrinsic + FDP weakness
• T1: intrinsic hand muscles (abductor pollicis brevis, interossei)
• MRI cervical spine confirms
• 25-year-old: less common but possible (disc herniation)

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7. Pancoast Tumor (Superior Sulcus Tumor)

• Lung apex tumor invading lower brachial plexus (C8/T1)
• Progressive hand intrinsic wasting
• Horner's syndrome (ptosis, miosis, anhidrosis) — highly specific association
• Usually painful (shoulder/arm pain)
• Sensory involvement of medial forearm/hand expected
• 25-year-old female: rare but must not miss — especially if smoker
• CXR, CT thorax, MRI brachial plexus

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8. Lower Brachial Plexopathy — Other Causes

• Radiation plexopathy (prior radiotherapy)
• Neoplastic infiltration (lymphoma, metastasis — less likely at 25)
• Neuralgic amyotrophy (Parsonage-Turner syndrome) — usually starts with severe pain, then weakness; sensory loss usually follows

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9. Spinal Muscular Atrophy (SMA) — Adult Onset

• SMA Type III (Kugelberg-Welander) / Type IV: onset in adulthood possible
• Pure LMN, symmetric or asymmetric, no sensory loss
• Proximal > distal typically, but distal hand involvement can occur
• Slowly progressive
• Genetic: SMN1 deletion/mutation
• Creatine kinase may be elevated

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10. Monomelic Motor Neuropathy — Hereditary (CMT Variants)

• Charcot-Marie-Tooth (CMT) — usually bilateral, but rare asymmetric presentations
• Distal hereditary motor neuropathy (dHMN): pure motor, distal wasting, no sensory loss
• Family history may be absent in sporadic cases
• Nerve conduction/genetic testing

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Less Likely in a 25-Year-Old Female (but to Exclude)

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Summary Table

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Priority Investigations

1. MRI cervical spine (with dynamic flexion views if Hirayama suspected) — exclude syrinx, Chiari, cord atrophy, disc herniation
2. EMG / Nerve conduction studies — localizes to anterior horn vs. root vs. plexus vs. peripheral nerve; identifies conduction block (MMN), characterizes denervation pattern
3. Chest X-ray / CT thorax — cervical rib, Pancoast tumor
4. Anti-GM1 IgM antibodies — MMN
5. Genetic testing (SMN1, PMP22) — if SMA or CMT suspected
6. Urine porphyrins — if episodic or occupational exposure
7. Serum CK — elevated in myopathic or neurogenic conditions
8. Blood lead levels — if occupational risk

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Unilateral Hand Wasting — Pure Motor Only (No Sensory)

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Anatomical Logic: Where Can a Purely Motor, Unilateral Lesion Sit?

Cortex / Corticospinal tract
    ↓  (UMN — wasting rare, no fasciculations)
Anterior Horn Cell  ←── Pure motor, unilateral = MOST SPECIFIC LEVEL
    ↓
Anterior (Motor) Root  ←── Pure motor if dorsal root spared
    ↓
Brachial Plexus lower trunk / medial cord
    ↓  (sensory usually co-involved, but minimal early)
Pure Motor Peripheral Nerve branch
    ↓  (deep palmar ulnar, AIN, PIN)
Muscle  ←── No sensory, but wasting pattern differs

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The Focused Differential (Unilateral, Pure Motor, Young Female, Subacute)

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1. ⭐ Hirayama Disease (Benign Monomelic Amyotrophy)

• 25-year-old, unilateral hand/forearm wasting, pure LMN, no sensory loss, no UMN signs, no pain
• C7–T1 anterior horn cell degeneration, confined to one limb
• "Oblique atrophy" — all intrinsic hand muscles + forearm flexors wasted, brachioradialis spared (C5/6 — above the lesion)
• Mini-polymyoclonus (finger tremor on extension) — characteristic
• Progression over 2–3 years then arrests spontaneously
• ♀ in Indian subcontinent: less gender bias than in Japan
• No fasciculations at rest typically (distinguishes from ALS)

• EMG: chronic + active denervation C7–T1, normal SNAPs
• MRI cervical spine in neutral AND flexion: asymmetric cord atrophy, loss of posterior dural attachment, anterior displacement of posterior dura on flexion, intramedullary T2 signal at C5–C8

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2. Syringomyelia (Early / Eccentric Syrinx)

• An eccentric syrinx can selectively destroy one side's anterior horn cells before crossing fibres or dorsal columns are involved — producing unilateral pure motor wasting
• Associated with Chiari I malformation (common in young women), post-traumatic, idiopathic
• Sensory loss (dissociated — pain/temp only, cape distribution) typically follows later
• Should always be excluded in any young person with unilateral hand wasting
• MRI spine: T2 hyperintense CSF-filled cavity; look for tonsillar descent (Chiari)

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3. Multifocal Motor Neuropathy (MMN)

• Pure motor, asymmetric, distal upper limb onset — classic presentation
• Mimics anterior horn cell disease but is demyelinating and treatable
• No sensory loss (distinguishes it from CIDP)
• Unilateral hand onset is well-described
• Anti-GM1 IgM antibodies (~50%)
• NCS: focal conduction block outside standard entrapment sites — pathognomonic
• Responds to high-dose IVIG — critical not to miss

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4. Pure Motor Focal Neuropathy (Compressive/Entrapment)

• Deep ulnar motor branch = most relevant for intrinsic hand wasting without sensory loss
• Cause: ganglion, repetitive pressure (cyclists, typists), occupational

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5. Neurogenic Thoracic Outlet Syndrome (True TOS)

• Anomalous fibrocartilaginous band, elongated C7 transverse process / cervical rib → compresses lower trunk (C8/T1)
• Wasting of intrinsic hand muscles, predominantly motor
• Sensory loss (medial forearm, 5th digit) is classically mild or absent — can appear pure motor
• Young women are disproportionately affected
• CXR: elongated C7 transverse process
• NCS/EMG: reduced CMAP ulnar > median; reduced SNAP medial forearm (if sensory affected at all)

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6. C8 or T1 Motor Root Compression (Radiculopathy — Motor Predominant)

• Cervical disc herniation compressing C8 or T1 root
• Dorsal (sensory) root can be spared if compression is purely anterior (ventral root lesion)
• Hand intrinsic wasting (T1) or FDP/FPL weakness (C8)
• Young adults: soft disc prolapse possible
• MRI cervical spine confirms

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7. Spinal Muscular Atrophy (SMA) — Focal / Asymmetric Variant

• Adult-onset SMA (Type III/IV) or distal hereditary motor neuropathy (dHMN) can start asymmetrically
• Pure LMN, no sensory loss — by definition
• Family history may be absent
• SMN1 gene testing; EMG shows widespread chronic denervation beyond clinically affected limb

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8. Monomelic Amyotrophy Secondary to Intrinsic Cord Lesion

• Intramedullary tumor (ependymoma, astrocytoma) at cervical cord level
• Selective anterior horn involvement before sensory tracts affected
• Rare but must be excluded with MRI

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What Makes This NOT ALS

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Ranked Summary

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Minimum Workup

1. MRI cervical spine — neutral + flexion (Hirayama), T2 (syrinx, Chiari, tumor, disc)
2. EMG + NCS — pattern of denervation, conduction block, SNAP intact?
3. Anti-GM1 IgM — MMN
4. CXR — cervical rib / elongated C7 transverse process
5. SMN1 gene test — if EMG shows widespread denervation beyond one limb

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Procedure in Meningitis with Raised ICP + CSF Collection in Hydrocephalus

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PART 1: Approach to LP in Suspected Meningitis with Raised ICP

The Core Dilemma

"Antibiotics should not be delayed awaiting successful lumbar puncture. Antibiotics will not affect PCR or bacterial antigen testing." — Rosen's Emergency Medicine

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Step 1 — Start Empirical Treatment IMMEDIATELY

If blood cultures can be drawn within 10 minutes — do so before antibiotics. If not feasible, give antibiotics first.

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Step 2 — Identify Features of Raised ICP / Risk of Herniation

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Step 3 — Performing the LP Safely When ICP is Raised

• No midline shift, no mass lesion, no herniation → LP can proceed, but with precautions
• Signs of herniation / large mass / obliterated cisterns → LP is contraindicated (see alternative CSF collection below)

Safe LP Technique When ICP is Elevated:

1. Position: Lateral decubitus (left lateral) — never sitting position when ICP is raised (sitting raises CSF pressure further at lumbar level)
2. Needle: Use a pencil-point (atraumatic) spinal needle (Whitacre 22G) — lower risk of post-LP herniation than cutting needle; smaller bore
3. Level: L3–L4 or L4–L5 interspace (below the conus at L1–L2)
4. Stylet IN: Always remove stylet slowly, never rapidly decompress
5. Measure opening pressure: Normal <20 cm H₂O; in meningitis often 20–40+ cm H₂O
6. Volume removed: Collect minimum volume necessary (3–4 tubes, ~8–12 mL total) — do not open tap and let CSF drain freely
7. Do NOT drain large volumes — risk of downward herniation
8. Mannitol cover: If opening pressure >40 cm H₂O or patient deteriorates during LP:
   • Stop immediately
   • Give Mannitol 0.5–1 g/kg IV over 20 minutes
   • Consider neurosurgical consult for EVD
9. After LP: Keep patient flat for 1 hour; monitor closely for signs of coning (Cushing's triad — hypertension, bradycardia, irregular respirations)

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Step 4 — Managing ICP in Meningitis (Adjunctive Measures)

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When LP is Absolutely Contraindicated in Meningitis

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PART 2: CSF Collection in Large / Obstructive Hydrocephalus

Option 1 — External Ventricular Drain (EVD) / Ventriculostomy

• Kocher's point (most common site): 1 cm anterior to the coronal suture, 2–3 cm lateral to midline (mid-pupillary line) on the non-dominant side
• Catheter placed into the frontal horn of the lateral ventricle
• Provides:
  1. Direct CSF sampling (ventricular CSF in meningitis) — highest diagnostic yield
  2. Continuous ICP monitoring
  3. Therapeutic CSF drainage to control ICP
• Note: ventricular CSF in meningitis may show higher cell counts, lower glucose, higher protein than lumbar CSF — interpret accordingly

Option 2 — Sampling Via Existing VP Shunt / Reservoir

• Shunt tap (by neurosurgeon or trained neurologist):
  • Insert 23–25G butterfly needle into the shunt reservoir under sterile conditions
  • Aspirate 2–3 mL CSF gently (do not aspirate hard — risk of pulling choroid plexus)
  • Send for cell count, protein, glucose, culture, sensitivity
  • Also culture the shunt hardware itself if shunt infection suspected
  • The shunt itself may be the source of infection (S. epidermidis, S. aureus — shunt meningitis)

Option 3 — C1–C2 Lateral Cervical Puncture (Cisternal Puncture)

• Performed under fluoroscopic guidance between C1 and C2 vertebrae
• Accesses the lateral cervical subarachnoid space
• Used when:
  • LP site infected / impossible
  • Communicating hydrocephalus but lumbar route blocked
  • Requires experienced operator (neurosurgery/interventional radiology)

Option 4 — Cisternal Puncture (Suboccipital)

• Needle inserted into the cisterna magna (suboccipital approach)
• Access between the posterior arch of C1 and the foramen magnum
• Rarely used; significant risk of brainstem injury if not performed by an expert
• Reserved for special circumstances (lumbar block, spinal deformity)

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Summary Flowchart

Suspected Meningitis
        |
        ↓
IMMEDIATELY: Blood cultures + empirical antibiotics + dexamethasone + aciclovir
        |
        ↓
Any risk features for raised ICP?
(focal signs, papilloedema, GCS≤12, immunocompromised, seizure)
        |
   YES  |   NO
        |         → LP immediately (lateral decubitus, thin needle, minimal volume)
        ↓
CT Brain STAT
        |
   No herniation   →   LP with ICP precautions
        |
   Herniation / obstructive hydrocephalus
        |
        ↓
NEUROSURGERY: EVD / shunt tap / Ommaya reservoir
        ↓
Ventricular CSF sent for analysis + culture
ICP controlled with EVD drainage

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Peripheral Vertigo vs. Central Vertigo

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Anatomy in Brief

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Master Comparison Table

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Nystagmus — The Key Discriminator

"Spontaneous nystagmus of peripheral origin is typically horizontal or horizontal-torsional and does not change direction with gaze. Spontaneous nystagmus of central origin can be purely vertical or torsional and usually changes direction with changes in gaze." — Cummings Otolaryngology

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The HINTS Exam (Bedside — For Acute Vestibular Syndrome)

HINTS positive for central = negative HIT + direction-changing nystagmus + skew deviation → stroke until proven otherwise → MRI DWI urgently

⚠️ HINTS should only be used in acute vestibular syndrome (constant vertigo); not valid in BPPV. Requires experienced examiner.

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Causes

Peripheral Vertigo Causes

Central Vertigo Causes

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Dix-Hallpike Test (Peripheral vs. Central Positional Vertigo)

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Clinical Danger Signs — "This is Central Until Proven Otherwise"

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Summary Mnemonic: "CENTRAL is DANGEROUS"

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Convulsive vs. Non-Convulsive Status Epilepticus

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Definition

• t1 (5 min) = treat now (abnormal, self-termination unlikely)
• t2 (30 min) = long-term neuronal injury begins

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Master Comparison Table

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Types (ILAE Classification)

Convulsive SE

• Generalized tonic-clonic SE — most dangerous; bilateral motor activity + LOC
• Focal motor SE (including epilepsia partialis continua) — unilateral jerking; consciousness may be preserved
• Tonic SE — sustained stiffening; often in Lennox-Gastaut
• Myoclonic SE with coma — post-anoxic; very poor prognosis

Non-Convulsive SE

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EEG Patterns

"The definitive diagnosis of NCSE requires EEG confirmation. Even CSE must be differentiated from psychogenic status epilepticus, which may require video-EEG." — Bradley and Daroff's

"8% of comatose patients in the ICU are found to be in NCSE — continuous EEG monitoring is essential." — Plum and Posner

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Clinical Clues to NCSE

• Prolonged postictal confusion (>30–60 min after apparent seizure cessation)
• Unexplained altered consciousness / encephalopathy in ICU
• Coma of unknown cause
• Subtle motor signs: eye deviation, repetitive eye blinking, facial twitching, subtle limb myoclonus
• "Waxing and waning" consciousness
• Known epilepsy with unexplained behavioural change
• Failure to regain consciousness after treatment of CSE → suspect subtle CSE / NCSE with coma

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Treatment Protocol

Phase 1 — Stabilization (0–5 min)

• ABC, IV access, O₂, glucose check (give 50 mL 50% dextrose if low + thiamine 100 mg IV)
• Vital signs, cardiac monitor

Phase 2 — Initial Therapy (5–20 min) — Benzodiazepines

Lorazepam 0.1 mg/kg IV controls CSE in 64.9% of cases within 20 min (VA Cooperative Study)

Phase 3 — Second-Line Agents (20–40 min, if benzodiazepines fail)

Phase 4 — Refractory SE (>40 min, failed 2 agents)

• Midazolam infusion 0.2 mg/kg bolus → 0.05–2 mg/kg/h
• Propofol 2 mg/kg bolus → 5–10 mg/kg/h (caution: propofol infusion syndrome)
• Thiopental/pentobarbital coma — burst-suppression target

Phase 5 — Super-Refractory SE (>24 h on anaesthetic infusion)

• Ketamine infusion
• Inhaled isoflurane
• Immunotherapy (steroids, IVIG, plasmapheresis — if autoimmune encephalitis suspected)
• Ketogenic diet
• Therapeutic hypothermia

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Key Differences — Crisp Summary

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Cryptococcal Meningitis

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Organism & Epidemiology

• Cryptococcus neoformans — encapsulated basidiomycete yeast; C. gattii in immunocompetent hosts
• Ubiquitous in soil, pigeon droppings; inhalation → primary pulmonary infection → haematogenous spread to CNS
• Most common AIDS-defining meningitis globally; most common cause of adult meningitis in Sub-Saharan Africa
• Occurs when CD4+ count <100 cells/μL in HIV; also affects transplant recipients, haematologic malignancies, high-dose steroids
• Universally fatal if untreated

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Pathophysiology

• Inhibits phagocytosis
• Reduces inflammation → CSF often has surprisingly few cells (minimal pleocytosis)
• Accumulates in Virchow-Robin spaces → gelatinous pseudocysts in basal ganglia
• Blocks CSF resorption → raised ICP — the primary cause of death and neurological damage

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Clinical Features

⚠️ Classic meningeal signs may be absent in >50% of immunocompromised patients. Think cryptococcal meningitis in any HIV patient with headache.

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MRI Brain

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Diagnosis

CSF Analysis — Key Tests

CSF Biochemistry (Typical Pattern)

Low CSF cell count + high antigen titre = poor prognosis (immune system not reacting)

Other Diagnostic Points

• Lateral flow assay (LFA) — point-of-care CrAg test; rapid, cheap, field-deployable
• β-D-glucan: NOT useful for Cryptococcus (useful for other fungi)
• Screen all HIV patients with CD4 <100 with serum CrAg before ART initiation

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Poor Prognostic Features

• Impaired consciousness at presentation
• Raised ICP / hydrocephalus
• CSF CrAg titre >1:1024
• Low CSF WBC (<20 cells/μL) — reflects poor host immune response
• Positive India ink on CSF
• High fungal burden
• Mortality: 10–25% in resource-rich settings; up to 43% in resource-poor settings

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Treatment

Phase 1 — Induction (2 weeks)

Liposomal AmB preferred over AmB deoxycholate — less nephrotoxicity

• AmB deoxycholate 0.7–1 mg/kg/day IV + fluconazole 800 mg/day

• Daily renal function, electrolytes (K⁺, Mg²⁺) — amphotericin causes nephrotoxicity, hypokalemia, hypomagnesemia
• FBC (flucytosine → bone marrow suppression, especially in HIV)
• Flucytosine levels if available (target 40–60 μg/mL)

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Phase 2 — Consolidation (8 weeks)

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Phase 3 — Maintenance / Secondary Prophylaxis

Without maintenance therapy → relapse in >50% of patients

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Management of Raised ICP (Critical)

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ART Timing in HIV (Critical — COAT Trial)

Starting ART within 1–2 weeks of beginning antifungal therapy increased 26-week mortality to 45% vs. 30% if ART delayed to 5 weeks (HR 1.73; COAT trial 2014)

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IRIS in Cryptococcal Meningitis

• Occurs weeks to months after ART initiation as CD4 count recovers
• Paradoxical worsening of symptoms (headache, fever, lymphadenopathy, neurological deterioration)
• Treat with corticosteroids (dexamethasone or prednisolone) + continued antifungals
• Do not stop ART

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Diagnostic Sensitivity Summary

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Crisp Summary

Cryptococcal Meningitis
     │
     ├── Who: HIV (CD4 <100), transplant, steroids
     ├── Organism: C. neoformans (encapsulated yeast)
     ├── Classic: headache + raised ICP ± minimal meningism
     ├── Diagnose: CSF CrAg (>90%) + India ink + culture
     │
     ├── TREAT:
     │   Induction (2 wks): Liposomal AmB 3–4 mg/kg/day + Flucytosine 100 mg/kg/day
     │   Consolidation (8 wks): Fluconazole 400 mg/day
     │   Maintenance: Fluconazole 200 mg/day until CD4 >200 × 6 months
     │
     ├── ICP: Daily therapeutic LPs → target normal pressure
     ├── ART: Delay ≥5 weeks (COAT trial)
     └── Mortality: 10–43% despite treatment

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MRI Basal Ganglia Lesions — Images & Differential Diagnosis

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How to Approach Basal Ganglia Lesions on MRI

1. Unilateral or bilateral?
2. What is the signal pattern? (T2 bright, T1 bright/dark, ring enhancing, non-enhancing)
3. Is there restricted diffusion (DWI)?
4. Clinical context? (Age, immunocompromise, toxic exposure, metabolic disease)

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Image Gallery

1. Cryptococcal Meningitis — Gelatinous Pseudocysts

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2. Cryptococcal Meningitis — Dilated Virchow-Robin Spaces (Perivascular Pseudocysts)

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3. Cerebral Toxoplasmosis — Ring-Enhancing Lesions in Basal Ganglia

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4. Autoimmune Encephalitis (LGI1) — T2 Shine-Through, No True Restricted Diffusion

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5. Wilson Disease — Bilateral Basal Ganglia T2 Signal Changes

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Differential Diagnosis of Basal Ganglia Lesions on MRI

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A. Bilateral Symmetric T2 Hyperintensity (Non-Enhancing)

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B. Unilateral / Focal T2 Hyperintensity ± Enhancement

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C. Non-Enhancing Punctate T2/FLAIR Bright Lesions in Basal Ganglia

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D. Autoimmune / Inflammatory

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Key Discriminating Points

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MRI Basal Cistern Exudates — Images & Differential Diagnosis

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Normal vs. Abnormal Basal Cisterns

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Image Gallery

1. Tuberculous Meningitis — Thick Basal Cistern Enhancement (Classic)

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2. TBM — Axial T1+Gad — Interpeduncular Cistern Obliteration

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3. TB Meningitis — Radiological Triad (Hydrocephalus + Basal Enhancement + Pachymeningitis)

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4. TBM — Active Basal Exudates Then Steroid Response (Sequential)

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5. Neurosarcoidosis — Nodular Leptomeningeal Enhancement at Basal Cisterns

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6. FLAIR Hyperintensity in Basal Cisterns (Non-specific but Sensitive)

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7. Leptomeningeal Carcinomatosis — "Sugar-Coating" (Zuckerguss) Appearance

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Differential Diagnosis of Basal Cistern Exudates/Enhancement

1. Infectious Causes (Most Common)

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2. Granulomatous / Inflammatory (Non-Infectious)

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3. Neoplastic

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4. Vascular / Other

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Key Discriminating Features

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Pathology of TBM Basal Exudates (Adams & Victor)

"A thick, gelatinous exudate accumulates at the base of the cerebral hemispheres, obliterating the pontine and interpeduncular cisterns and extending to the meninges around the medulla, the floor of the third ventricle, the optic chiasm, and the undersurfaces of the temporal lobes... Cranial nerves are often involved far more often than with typical bacterial meningitis. Arteries may become inflamed and occluded, with infarction of brain."

1. Dense basal cistern enhancement
2. Communicating hydrocephalus (cistern blockage)
3. Cerebral infarcts (endarteritis of perforators)

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