Sensory ataxia
Tabes dorsalis: This late meningoradiculitis form of neurolues is often refered to as progressive locomotor ataxia. The rise in incidence of sexually transmitted diseases and HIV has been accompanied by a resurgence in the incidence of neurosyphilis. Two years or more after exposure to syphilis a period of tertiary syphilis develops with tabes dorsalis being one of the manifestations. The initial symptoms consist of diplopia due to paralysis of the 3rd, 4th, or 6th cranial nerves, irregular pupils, paresthesia and hyperesthesia. Pupillary abnormalities (including Argyll-Robertson pupil) are present in 90% of patients. Ptosis and poor facial tone can develop as a result of cranial neuritis and produces the tabetic facies. Patients may also complain of lightning pains mainly in the extremities although no part of the body is spared. Visceral crisis is sometimes seen and patients may complain of abdominal, rectal, and laryngeal pain. Because of involvement of the dorsal root ganglia and posterior columns there is loss of vibratory and position sense in the legs. Analgesia may be seen over the breasts, medial sides of the forearms, lateral aspects of the legs, and perianal regions (Hitzig lines). As the condition progresses, difficulties in coordination and balance develop. These are worse in the dark but are also present when the patient has good visual input. The syndrome is also characterized by the loss of reflexes in the legs, sphincter dysfunction, and sexual dysfunction. The loss of sensation which occurs in the legs may lead to Charcot joints. CSF protein and pleocytosis may be elevated in early disease, but later in the course, return to normal. The serum RPR is usually reactive at a dilution of less than or equal to 1:16, but it may be negative late in the disease. The serum MHA-TP (or the FTA-ABS) is positive; a negative result essentially excludes the diagnosis of tabes dorsalis. In the early stages, the CSF VDRL is abnormal and the WBC count is elevated; most of the cells are mononuclear. In later, burned out cases the VDRL may normalize and the cell count may be normal. The CSF protein is usually elevated to more than 100 mg/dl in active disease, but slowly returns towards normal as the disease "burns out". After an intensive penicillin course (Pen G for 3 weeks), quantitative blood serology is determined at 3 month intervals and usually shows a decline in titer. The CSF is examined at 6 and 12 months. If not normal, CSF is reexamined at 2 years. After 3 years, if the patient has improved and is clinically stable, and if the CSF and serological tests are normal, neurological and CSF examinations are discontinued. Retreatment is recommended with high doses of iv Penicillin G under the following circumstances if: 1) clinical neurological findings progress without finding another cause, especially if CSF pleocytosis persists, 2) the CSF cell count is not normal at 6 months, 3) the VDRL test in the serum or CSF fails to decline or shows a four fold increase; 4) the first course of treatment was suboptimal. The degree of recovery depends on the extent of the disease at the time of starting treatment, but is usually minimal.
Hereditary
spinocerebellar ataxia (SCA-1 and SCA-8):
SCA formerly called autosomal dominant cerebellar ataxia (ADCA), has a
prevalence of 1-5/100,000 in the general population. There is substantial
geographical distribution of the different forms of SCA: e.g. SCA-3 is very
prominent in Portuguese/Azorean and Dutch families. In
contrast to autosomal recessive ataxias, SCA almost consistently develop after
the age of 25 years.
These SCAs share the primary clinical features of cerebellar syndrome with
additionally supranuclear ophthalmoplegia, slow eye movements,
optic neuropathy, subcortical dementia, extrapyramidal deficits, dysphagia,
pyramidal signs, amyotrophy and peripheral neuropathy. On clinical criteria
alone, they are often indistinguishable and one patient would fit to different
categories. The classification of ADCA based on clinical and neuropathologic
features was therefore used and divided ADCAs into three different groups (ADCA
I-III) based on associated signs.
SCA-1
and -3 can be allocated to ADCA I being: progressive cerebellar gait and limb
ataxia with pyramidal and extrapyramidal involvement, slow saccadic eye
movements, supranuclear ophthalmolegia, hyporeflexia and dementia. Onset in 4th
decade of life and disease duration of 15 years.
SCA-8: This form of autosomal dominant spinocerebellar ataxia presenting with mild truncal and limb ataxia, scanning dysarthria, impaired smooth pursuit and horizontal nustagmus, spastic paraparesis and reduced vibration, and is mapped to 13q21. Slowly progressive wheelchair bound in the 4th and 5th decades.
Subacute combined degeneration of the spinal cord (SACD): Vitamin B12 deficiency leads to SACD. High-risk groups for the deficiency syndrome include the elderly, defective intrinsic factor production by gastric parietal cells (pernicious anemia), patients taking ulcer medications over long periods, heavy abuse of nitrous oxide, patients with AIDS, vegetarians, patients who have undergone stomach resection or small bowel resection, or both, and patients with dementia. The onset of symptoms is usually insidious, with paresthesias in the hands and feet present in the majority of patients. Sensory peripheral neuropathy can be the sole manifestation of B12 deficiency. Paresthesias in the feet and distal loss of all modalities of sensation with loss of ankle jerks are observed. Symptoms improve after therapy with B12. The next most common complaints include weakness and unsteadiness of gait. Cerebral symptoms may occur and can include confusion, delusions, hallucinations, mental slowing, and depression. Loss of position or vibration sense is the most common abnormality. Motor impairment may range from only mild clumsiness to a spastic paraplegia. Visual impairment can be seen; ophthalmological exam may show bilateral visual loss, optic atrophy, and centrocecal scotomata. Brainstem or cerebellar signs or even reversible coma may occur. Hematological abnormalities, including hypersegmentation of polymorphonuclear cells and a macrocytic anemia, can be seen; however, they may be completely absent at the time of neurological presentation. Current state-of-the-art testing uses serum cobalamin levels as a screening test, and the Schilling test, serum or urine methylmalonic acid and homocysteine determinations as confirmatory tests. A Schilling test detecting impaired intestinal absorption of vitamin B12, should be performed if there is enough clinical suspicion for the disease, and may reveal low vitamin B12 absorption even when the serum level is normal. The presence of circulating antibodies to parietal cells in many of these patients suggests an underlying autoimmune disorder. MRI reveals confluent leukoencephalopathy, even in the absence of anemia or myelopathy. VEP and SEP are frequently abnormal. SNAPs are absent or reduced in about 80% of patients and motor NCVs show axonal and demyelinating features. A typical regimen consists of intramuscular vitamin B12 injections of 1 mg twice weekly for 2 weeks, followed by monthly injections of 1 mg. For patients whose Schilling test demonstrates malabsorption of vitamin B12, monthly 1 mg injections should be continued on a lifelong basis. There is no evidence that overdosing can speed neurologic recovery; adverse reaction to high doses of vitamin B12 is unknown.
Friedreich ataxia (FA): This form of ataxia is the most common hereditary form (autosomal recessive with variable phenotype) with a frequency of 1/50,000 in the population. Essential diagnostic criteria include its onset before the age of 25 years and <5 years after onset the development of the following: progressive gait ataxia, early areflexia in lower limbs, vibration and joint position sensory deficits, extensor plantar responses, and motor nerve conduction velocity >40 m/s in upper limbs with small or absent SNAPs consistent with axonal sensory neuropathy. Other features are scoliosis, club feet, cardiomyopathy (>50%), diabetes or impaired glucose tolerance (10%) and dementia. Optic neuropathy and deafness occurs in less than 25% of cases. Life expectancy of FA is on average 35 years, death occurring from heart failure. The locus is mapped to chromosome 9q13-q21.1 (frataxin). Frataxin results in intramitochondrial iron accumulation, which explains why FA is now considered a mitochondrial disorder. Abnormal ECG and echocardiography are seen in approximately 60% of cases. CSF is normal. The condition most frequently confused with FA is HSMN I. This demyelinating form of HSMN, is essentially characterized by autosomal dominant inheritance with slow conduction velocities (always <40 m/s). Late-onset FA (after the age of 25 years) (LOFA) is characterized with a slower progression and lower incidence of skeletal deformity. Investigations should include brain MRI, serum vitamin E and B12 levels, and a-fetoprotein levels and DNA analysis to detect GAA trinucleotide expansion.
Abetalipoproteinemia or Bassen-Kornzweig syndrome: Almost 50% of patients with abetalipoproteinemia present with neurological manifestations. Age of onset is usually in the 1st or 2nd decades of life. Loss of night vision and steatorrhare are frequently the earliest symptom and precede weakness of the limbs with areflexia and sensory ataxia, later followed by cerebellar ataxia. Steatorrhea causing vitamin (A, E and K) malabsorption results in progressive unremitting spinocerebellar ataxia with loss of proprioception and vibratory sensory loss (tabetic type of sensory ataxia), areflexia and weakness (vitamin E responsive peripheral neuropathy), INO with nystagmus of adducting eye and retinitis pigmentosa (in later stages). Gastrointestinal symptoms may be mild or subclinical. ESR is low. Fresh blood smear with acanthocytes with hypolipidemia (reduced serum total cholesterol, apoprotein B (necessary for chylomicron formation), absent b-lipoprotein and low or absent chylomicrons, LDL-cholesterol and VLDL (essential for vitamin E transport)), low levels of plasma prothrombin, very low vitamin E and low serum levels of other fat soluble vitamins (except vitamin D which has its own transport system) are diagnostic. Urinary mevalonic acid levels are increased. NCVs reveal axonal neuropathy. SSEPs, VEP and ERG are abnormal. Sural nerve biopsy shows diminished numbers of myelinated fibers. The disease is autosomal recessive and caused by deficiency of microsomal triglyceride-transport protein (MTP gene mapped to chromosome 4q22-24). PET scan shows reduced [18F]dopa uptake in both putamen and caudate nucleus in severe and prolonged vitamin E deficiency. By the 2nd or 3rd decades patients are often bedridden. The syndrome needs to be differentiated from FA. Familial hypobetalipoproteinemia: Homozygous patients are clinically indistinguishable from patients with abetalipoproteinemia. They generally have low levels of apoprotein B, betalipoproteins, total cholesterol and LDL-cholesterol, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome). Heterozygous patients are usually asymptomatic are have part of the syndrome. The disorder is autosomal dominant and is caused by mutations in the apoprotein B gene (chromosome 2p24).