10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders

1. Classifying Neuropathy

The first question is distribution, because it separates entirely different differentials.

Mononeuritis multiplex is the red-flag pattern. Stepwise involvement of individually named nerves signals a vasculitic process — polyarteritis nodosa, ANCA-associated vasculitis, cryoglobulinemia — and requires urgent evaluation, since untreated vasculitic neuropathy causes permanent deficits.

Initial laboratory evaluation of an unexplained polyneuropathy: fasting glucose or hemoglobin A1c (with an oral glucose tolerance test if impaired glucose tolerance is suspected), vitamin B12 with methylmalonic acid, thyroid-stimulating hormone, complete blood count, comprehensive metabolic panel and serum protein electrophoresis with immunofixation to detect a monoclonal gammopathy.

2. Common Entrapment Neuropathies

Two discriminations the exam uses:

• Carpal tunnel syndrome spares palmar sensation, because the palmar cutaneous branch of the median nerve arises proximal to the tunnel. Numbness of the whole palm suggests a more proximal median lesion or a C6-C7 radiculopathy.
• Foot drop from fibular neuropathy preserves inversion (tibial nerve). Foot drop with weak inversion implicates the L5 root, not the fibular nerve.

Carpal tunnel associations that should be sought: pregnancy, hypothyroidism, diabetes, obesity, rheumatoid arthritis, acromegaly and amyloidosis — bilateral carpal tunnel syndrome in an older man with cardiac findings should raise transthyretin amyloidosis.

3. Diabetic and Painful Neuropathies

Diabetic polyneuropathy is the most common neuropathy in developed countries: symmetric, distal, sensory-predominant, with burning pain, numbness and loss of ankle reflexes and vibration sense. Complications include painless foot ulceration and Charcot neuroarthropathy, which is why annual monofilament foot examination matters.

Diabetic autonomic neuropathy produces gastroparesis, orthostatic hypotension without compensatory tachycardia, erectile dysfunction, and silent myocardial ischemia.

Diabetic amyotrophy (lumbosacral radiculoplexus neuropathy) causes severe unilateral thigh pain with proximal weakness and weight loss, and typically improves over months.

Treatment of painful neuropathy: glycemic control slows progression in type 1 diabetes but has limited effect in type 2. Symptomatic agents include duloxetine, pregabalin, gabapentin and tricyclic antidepressants. Opioids are not first-line and are avoided for chronic neuropathic pain.

Postherpetic neuralgia — an enumerated blueprint topic — is pain persisting beyond about three months after the zoster rash. Risk rises steeply with age. Recombinant zoster vaccination is the primary prevention, and prompt antiviral treatment of acute zoster reduces, but does not eliminate, the risk. Treatment uses gabapentinoids, tricyclics and topical lidocaine.

4. Central Nervous System Tumors

Enumerated under both Neurology and Medical Oncology, listing brain tumors, spinal cord tumors and compression, carcinomatous meningitis and paraneoplastic syndromes.

In adults, metastases outnumber primary brain tumors, arising most often from lung, breast, melanoma, renal and colorectal primaries; melanoma metastases are notably prone to hemorrhage.

Presentations: progressive headache that is worse in the morning or with Valsalva, new-onset seizure in an adult, progressive focal deficit, or personality change. Corticosteroids reduce vasogenic edema and often produce rapid symptomatic improvement, but should be deferred when primary CNS lymphoma is suspected until tissue is obtained, because steroids can transiently dissolve the lesion and render biopsy non-diagnostic.

Carcinomatous (leptomeningeal) meningitis presents with multifocal neurologic findings at different levels of the neuraxis — cranial neuropathies plus radicular symptoms plus headache — and is diagnosed by cerebrospinal fluid cytology, which frequently requires repeated large-volume sampling, with MRI of the whole neuraxis.

Malignant spinal cord compression is the emergency in this group. New or worsening back pain in a patient with known cancer is cord compression until proven otherwise. Pain typically precedes neurologic findings by weeks — that interval is the opportunity. Give corticosteroids immediately on suspicion and obtain urgent MRI of the entire spine, since multiple non-contiguous levels are common. Neurologic status at the time of treatment is the strongest predictor of eventual ambulation.

Paraneoplastic neurologic syndromes include Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, limbic and other autoimmune encephalitis, and opsoclonus-myoclonus; they may precede the cancer diagnosis by months and warrant a directed tumor search.

5. Disorders of Cerebral Function

Enumerated as dementia, aphasia and medical causes of delirium. Dementia and delirium are covered in the geriatrics chapter; the aphasia syndromes are worth a table because they localize precisely.

Wernicke aphasia is frequently mistaken for delirium or psychosis, because the patient speaks fluently but nonsensically and cannot follow commands. The clue is that other cognitive domains and the level of consciousness are intact.

6. Other Neurologic Disorders

A named blueprint subsection listing neurocutaneous syndromes, head injury, spinal cord injury and disorders, idiopathic intracranial hypertension, motor neuron disease, neuroleptic malignant syndrome and cerebellar ataxias.

Head injury

Concussion is a clinical diagnosis with normal imaging. Most symptoms resolve within days to weeks; a graduated return-to-activity protocol is used and an athlete should never return to play on the day of injury.

Chronic subdural hematoma is the diagnosis not to miss in older adults: weeks of progressive confusion, headache or gait disturbance after trivial or forgotten trauma, with anticoagulation, alcohol use and cerebral atrophy as risk factors. It is a reversible cause of cognitive decline and is the reason neuroimaging is included in a dementia workup.

Epidural hematoma classically follows temporal bone fracture with middle meningeal artery injury and a lucid interval; it is a neurosurgical emergency.

Spinal cord disorders

Cord compression from tumor, epidural abscess, hematoma or disc requires emergent MRI. Cauda equina syndrome — urinary retention (the most sensitive finding), saddle anesthesia, bilateral leg weakness, decreased rectal tone — requires emergent imaging and decompression.

Subacute combined degeneration from vitamin B12 deficiency damages the dorsal columns and corticospinal tracts, producing loss of vibration and proprioception with upper motor neuron signs and paradoxically absent ankle reflexes from coexisting neuropathy. It may occur without anemia or macrocytosis, and nitrous oxide exposure — including recreational use — can precipitate it. Copper deficiency produces a nearly identical myeloneuropathy.

Syringomyelia produces a cape-like dissociated sensory loss, with loss of pain and temperature but preserved light touch and proprioception, from involvement of the crossing spinothalamic fibers.

Cerebellar ataxias

Causes include alcohol (vermian degeneration with gait ataxia and relatively spared arms), phenytoin toxicity, Wernicke encephalopathy (ataxia, ophthalmoplegia and confusion — give thiamine before glucose), paraneoplastic cerebellar degeneration, hypothyroidism, and hereditary ataxias including Friedreich ataxia and the spinocerebellar ataxias.

Neurocutaneous syndromes

Neurofibromatosis type 1 — cafe-au-lait macules, axillary and inguinal freckling, neurofibromas, Lisch nodules, optic glioma. Neurofibromatosis type 2 — bilateral vestibular schwannomas, meningiomas. Tuberous sclerosis — ash-leaf macules, facial angiofibromas, shagreen patch, seizures, subependymal nodules, renal angiomyolipomas. Sturge-Weber syndrome — port-wine stain in the trigeminal distribution with leptomeningeal angioma and seizures.