Familial Spastic Paraplegias

The FSPs, also known as Strumpell-Lorrain syndrome and hereditary spastic paraplegias, are a broad group of

TABLE 36-3 -- SELECTED DIFFERENTIAL DIAGNOSIS OF MOTOR NEURON DISEASES OF CHILDREN ACCORDING TO SOME PRESENTING SYMPTOMS

HYPOTONIA

PROGRESSIVE MUSCLE WEAKNESS

Hereditary motor and sensory neuropathies

Peripheral neuropathies

Neuromuscular transmission defect

Subacute inflammatory polyradieuloneuropathy

Transient neonatal myasthenia

Congenital myasthenic syndromes

Hereditary motor neuropathies

Muscular dystrophies

Infantile botulism

Metabolic myopathies

Congenital myopathies with distinguishing structural abnormalities

Glycogen storage diseases

Lipid storage myopathies

Inflammatorty myopathies

Central core disease

Dermatomyositis/polymyositis

Nemaline myopathy

PROGRESSIVE CRANIALNERVE PARALYSIS

Centronuclear myopathy

Muscular dystrophies

Metabolic myopathies

Neoplasms

Glycogen storage diseases

Brain stem glioma

Lipid storage myopathies

Extnnsic postenor fossa tumor

Mitochondrial myopathies

Nasopharyngeal neoplasm

Inflammatory myopathies

Neuromuseular transmission defeet

Dermatomyositis/polymyositis

Bohllism

Connective tissue disorders

Myasthenia granis

Osteogenesis imperfecta

Congenital myasthenic syndromes

Marfan's disease

Ehlers-Danlos syndrome

Myopathies

Metabolic diseases

Ocular myopathies

Aminoacidopathies

Ophthalmoplegia plus syndromes

Organicacidurias

Renal reabsorption defects

Intracranial infections

Endocrnopathies

Tuberculosis

Prader-Willi syndrome

Nutritional disorders

genetically and clinically diverse disorders characterized by lower extremity spasticity and weakness. Generally, they are classified according to mode of inheritance and symptoms. The more common uncomplicated or so-called pure FSP indicates progressive spasticity of the lower extremities that may be accompanied by a mild decrease in proprioception and urinary sphincter dysfunction, whereas complicated FSP denotes the presence of other neurological problems.

Pathogenesis and Pathophysiology. Information about the genetic basis for these disorders is mushrooming. It has been established that uncomplicated autosomal dominant, autosomal recessive, and X-linked FSPs are heterogeneous disorders. Because families with strong similarities in phenotype are linked to different genetic loci, there may be various points of disturbance in a common biochemical pathway that leads to degeneration of the most distal portions of the longest ascending and descending central nervous system axons, particularly the corticospinal tracts from the motor cortex to the legs, the fasciculus gracilis fibers, and the spinocerebellar fibers (,iXable,36z4 ). Genetic penetrance is age dependent and nearly complete. [17]

Clinical Features and Associated Disorders. The patient generally presents with leg stiffness, weakness in the hip flexors, and impaired foot dorsiflexion in the second through fourth decades, although symptoms may be apparent in infancy or not until late adulthood. The gait disturbance progresses insidiously and continuously. Patients may also have paresthesia and mildly decreased vibratory sense below the knees, and urinary urgency and incontinence late in the disease. On neurological examination, generally there are no abnormalities of the corticobulbar tracts or upper extremities, except possibly brisk deep tendon reflexes. In the lower extremities, deep tendon reflexes are pathologically increased and there is decreased hip flexion and ankle dorsiflexion. Crossed adductor reflexes, ankle clonus, and extensor plantar responses are present. Hoffman's and Tromner's signs, as well as pes cavus, may be present. Occasionally, slight dysmetria may be seen on finger-to-nose testing in patients with longstanding disease.

The designation complicated FSP indicates spasticity with additional neurological impairment, such as optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. [17]

Differential Diagnosis and Evaluation. The FSPs are diagnoses of exclusion. Particular care is necessary if the family history is not revealing or if there are numerous complications or atypical features. Because FSP can mimic treatable disorders, such as vitamin B12 deficiency, doparesponsive dystonia, cervical spondylosis, or multiple sclerosis, exhaustive evaluation is justified. [17]

Molecular diagnosis is available only to family members within kindreds who have been linked to one of the identified loci. Electrophysiological studies are the most revealing. Somatosensory evoked potentials of the lower extremities show conduction delay in the dorsal column fibers, whereas cortical evoked potentials show reduced conduction velocity and amplitude in lumbar spinal segment muscles. Cortical evoked potentials of the arms are either normal or mildly slow. Nerve conduction studies are most often normal, although there may be subclinical sensory impairment of peripheral nerves and spinal pathways.

MRI of the brain and spinal cord as well as plasma long chain fatty acid analysis should be performed. [17]

Management and Prognosis. There is no treatment available to address the underlying process in FSP. Treatments to combat the problems associated with chronic paraplegia can be helpful, particularly oral or intrathecal baclofen or oral dantrolene for the lower extremity spasticity, and oxybutynin for bladder spasticity. Caution should be exhibited in counseling regarding the course of the disease because there is variation in severity of phenotype reported.

At this time, although the phenotypes of the various autosomal dominant FSPs are very similar, it does seem to be more severe in the families linked to chromosome 15q, in which more patients require wheelchairs by the fourth decade. The families linked to chromosome 2p showed more variation, including a less common childhood onset and a relatively nonprogressive course. U

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