Idiopathic small fiberpainful sensory neuropathy: This condition represents the most common type of painful sensory neuropathy in patients older than 50 years of age. Tendon reflexes, strength, sensation of position and vibration are normal. There is however reduced pinprick sensation in the lower limbs. Blood tests, EMG and NCVs are normal. Sudomotor function is reduced. Skin biopsy is abnormal. In most cases, no underlying cause can be found.
Hereditary neuropathies: These are generally associated with a positive family history and clinical examination shows pes cavus, reduced tendon reflexes and reduced distal sensation. Blood tests are normal while EMG and NCVs are abnormal.
Connective tissue-related peripheral neuropathy: These are associated with SLE, MCTD, RA, Sjögren syndrome. Reduced tendon reflexes and reduced distal sensation. EMG and NCVs are abnormal. ANA, ENA or RA may be positive.
Mononeuritis multiplex (vasculitis)
Paraneoplastic sensory neuronopathy: Women are more commonly affected than men. The neuronopathy precedes the tumor symptoms by 6 months - 3 years and develops subacutely over weeks and then stabilizes. Peripheral neuropathy is the presenting symptom in 95% of patients, while CNS and autonomic neuropathy present in 40% and 30% of patients, respectively. The course of the neuropathy is usually subacute (55%) or progressive (40%). Clinically, the neuropathy is mostly sensory (sensory ataxia) (70%) or sensorimotor (25%). At onset, symptoms are symmetrical (65%), asymmetrical (25%) or multifocal (10%) with pain (uncomfortable paresthesias) as a predominant manifestation (80%). The arms are most commonly affected often in an asymmetric way. Impairment of all sensory modalities, gait ataxia and areflexia are common Amyotrophia and fasciculations are rare and strength is normal. Occasionally they coexist with limbic encephalitis (encephalomyeloneuritis). Electrophysiology showed the axonal/neuronal pattern to be the most frequent (50% of studied nerves) with reduced or absent SNAPs and normal CMAP. In patients with sensory neuropathy, 88.5% of sensory nerves are abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves are abnormal. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and sensorimotor neuropathy. The CSF is usually lymphocytic with raised protein. Serum and CSF may contain high titers anti-Hu antibodies.
Amyloid neuropathies: primary and familial amyloidosis
Uremic polyneuropathy: 50% of patients with end-stage chronic renal failure have clinical or electrophysiologic evidence of polyneuropathy. Uremic polyneuropathy develops gradually and occurs with glomerular filtration rates below 10 ml/min. In contrast to the underlying causes of renal failure, which are often resulting in focal or demyelinating polyneuropathy, uremic polyneuropathy is axonal in nature. Restless legs (burning paresthesias, itching sensation) are often the initial manifestation, followed by muscle cramps and fatigability and, finally, muscle distal weakness and atrophy. Autonomic features are impotence and postural hypotension (most marked at times of fluid removal by dialysis). The earliest objective signs are loss of vibration at the toes and absent ankle jerks. NCVs indicate axonal degeneration of motor and sensory fibers. Renal transplant greatly improves the condition. Occasionally an acute uremic polyneuropathy may develop that resembles GBS. Most patients are diabetics in stable end-stage renal failure that is being treated with peritoneal dialysis. NCVs may show demyelinating features and raised CSF protein.
Hereditary sensory autonomic neuropathy
Chronic arsenic neuropathy: This type of poisoning occurs either acute or chronic (smelting workers). Subacute polyneuropathy (7-14 days) presenting as numbness and often painful paresthesias with loss of vibration and position sense are the initial manifestations, subsequently followed by leg muscle weakness. Ankle jerks are invariably lost. SNAPs are absent and motor conduction is initially mildly slowed. Sural nerve biopsy shows axonal degeneration. Improvement over years occurs but is often incomplete. Other features in acute poisoning are encephalopathy, pancytopenia, eosinophilia, liver and/or kidney failure depending on the amount. Chronic arsenic exposure in industrial workers may produce an asymptomatic sensorimotor neuropathy detectable only by NCVs. Mees lines and sole hyperkeratosis develop. CBC reveals anemia with basophilic stippling.
Anderson-Fabry disease (AFD): This X-linked recessive disorder of glycosphingolipid metabolism is due to a deficiency of the lysosomal enzyme alpha-galactosidase A with accumulation of neutral glycosphingolipids within the lysosomes of endothelial, perithelial, and smooth muscle cells of the myocardial and renal systems. The average age at onset is highly variable, but the diagnosis is usually made around the age of 20 years. A majority of homozygous men develop severe multisystemic disease (classic form), characterized by cutaneous angiokeratomas, renal failure (30%), progressive neurological (sensorineural deafness (78%), burning neuropathic pain (acroparesthesias) and paresthesias distally in the limbs provoked by exercise or heat (77%), cerebrovascular complications (24%)) and cardiac involvement (dysrhythmias and structural abnormalities apparent on echocardiography). The average age at onset of cerebrovascular symptoms is around 30 years for hemizygous individuals and 40 years of heterozygous. The most frequent symptoms and signs are, in descending order of frequency: hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, headache, hemiataxia, and ataxia of gait, in the hemizygous group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygous group. Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. The NCVs show significantly decreased amplitudes of motor and sensory NCVs. For the hemizygous, the recurrence rate for cerebrovascular disease is 76% and the death rate 55%; 86% of the heterozygotes have recurrent cerebrovascular event(s) and 40% die. The cerebrovascular manifestations of AFB, in both hemizygous and heterozygous, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and have a poor prognosis. Nevertheless, some affected men retain sufficient enzyme activity and remain asymptomatic for a long time; their main manifestation is hypertrophic cardiomyopathy. Female heterozygous carriers are usually asymptomatic; 15% of them, however, have severe involvement of one or several organs. Laboratory, histologic and molecular diagnosis identifies 100% of hemizygous and over 80% of heterozygous subjects. The median cumulative survival was 50 years. Biochemical diagnosis is based on a decreased level of plasma, tears, leucocyte or cultured fibroblasts a-galactosidase A activity. In addition, skin biopsy with ultrastructural examination of small blood vessels may be diagnostic. The gene is mapped to chromosome Xq22.
Celiac disease (or gluten sensitive enteropathy): The age of onset may vary between 40 - 80 years and the mean duration of ataxia between 3 to 25 years. Half of the patients do not present with gastrointestinal symptoms (gluten-sensitive enteropathy or celiac disease). Neurologic manifestations and dermatitis herpetiformis can occur without histologic evidence of bowel involvement. Majority of patients presenting with neurologic symptoms have peripheral neuropathy (often painful sensory neuropathy) or cerebellar ataxia ("gluten ataxia"). Other neurological features may include episodic unilateral headache with visual disturbances (hemianopia), deafness, encephalopathy (confusion, agitation, dementia), myelopathy, cerebral calcification and seizures. Some patients develop Ramsay-Hunt syndrome. The diagnosis is based on small bowel biopsy or the presence of serum IgA anti-gliadin and IgA endomysial antibodies. Up to 90% of patients with celiac disease are HLA DQ2, the remaining have DQ8 or DQ1. Brain MRI abnormalities vary from confluent areas of high signal throughout the white matter to foci of high signal scattered in both hemispheres. Only 33% of patients presenting with neurologic dysfunction associated with gluten sensitivity also have celiac disease. Gluten ataxia accounts for 40% of cases of idiopathic sporadic and familial cerebellar degeneration. The neurological manifestations may not respond to a gluten free diet.