Oculopharyngeal muscular dystrophy in Hispanic New Mexicans.

CONTEXT: Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico. OBJECTIVE: To characterize the clinical, genetic, and demographic features of the OPMD population in New Mexico. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with analysis of outpatient clinic medical records from 1965 to 2001 at the University of New Mexico Hospital and the New Mexico VA Health Care System in Albuquerque, which serve the entire state. MAIN OUTCOME MEASURES: Clinical phenotype, supplemented with genetic confirmation (n = 10 patients) and in-depth clinical evaluations (n = 49 patients). RESULTS: We identified 216 cases of OPMD (99 women and 117 men) from 39 kindreds of New Mexicans spanning up to 4 generations. All patients were Hispanic, and the majority of probands came from northern New Mexico. In patients who had both ocular and pharyngeal muscle weakness, ptosis was just as likely to occur before or concurrent with dysphagia. Proximal limb muscle weakness and gait abnormalities were common and occurred later than ocular or pharyngeal weakness. The clinical expression of OPMD caused marked debility, although life-table analysis showed no decrease in life expectancy compared with unaffected family members (P =.81). Ten individuals from different kindreds were found to have an identical polyalanine triplet repeat expansion ([GCG](9)) in the PABP2 gene. CONCLUSIONS: Individuals in this cohort had clinical and genetic characteristics of classic OPMD. Longevity was not affected, but patients experienced considerable morbidity. The origin of the PABP2 mutation in New Mexican OPMD patients is unclear, although the geographic and genetic isolation of northern New Mexicans with a long ancestry in this region may have contributed to the development of this cohort. This disease cohort represents a large and previously unrecognized health care issue in the state of New Mexico and should serve to raise the awareness of this disorder among clinicians who treat Hispanics in the Southwest and throughout the United States.

A commentary on 10 years of aldose reductase inhibition for limited joint mobility in diabetes.

This investigation examines the clinical response to long-term treatment of the diabetic syndrome of limited joint mobility (LJM) using an aldose reductase inhibitor (ARI) in comparison to historical controls, and proposes a potential role of aldose reductase (AR) genotype and expression in the clinical response to ARI. Clinical parameters, including quantitative hand movement and electromyogram, were followed over a decade of continuous ARI treatment with sorbinil (400 mg/day) in two patients with insulin-dependent diabetes mellitus (IDDM) and severe compromising LJM, and compared to the published 10-year prospective investigation of untreated IDDM diabetic patients with LJM. Both subjects were homozygous for the Z-2 AR allele (A-C)23 that has been linked with microvascular complications of DM. Cellular AR mRNA/beta-actin ratios for both treated patients while on ARI therapy were approximately one-half the value observed in untreated patients with the complications of nephropathy or neuropathy. This is the longest reported experience of ARI intervention for any diabetic complication, documenting sustained correction of LJM, lack of side effects, and a potential molecular basis for the therapeutic response.

Sural nerve water in vivo in normal humans measured by magnetic resonance spectroscopy: relation to age, height, gender, and neurological profile.

To enable the quantitative assessment of peripheral nerve structure and function, we determined the normal values for sural nerve hydration structure as measured by magnetic resonance proton imaging, and for neurological function with scores for neuropathic symptoms, signs, and nerve conduction properties. Normal human sural nerves contain 24.8 +/- 3.4% water. The structural water content of the nerves did not vary systematically in relation to age, height, gender, sural nerve conduction, neurologic symptoms, or examination deficits. In contrast, the neurological function scores were significantly influenced by age and selectively by height. Both nerve structure and function were stable over a 1-year interval. Measurement of human sural nerve water content in vivo by magnetic resonance proton imaging, and quantitation of the neurological profile of symptoms, signs, and conduction velocity are useful, noninvasive tools for the investigation of diseases in which changes in nerve structure may be related to alterations in nerve function.

Human type A botulism and treatment with 3,4-diaminopyridine.

3,4-diaminopyridine was evaluated for its ability to improve muscle strength, respiratory function and electromyographic compound muscle action potentials in human botulism. In a double blind, placebo controlled study, 3,4-diaminopyridine failed to improve these parameters in a 31-year old patient with severe food-borne type A botulism. The addition of an anti-cholinesterase medication to the 3,4-diaminopyridine did not add any benefit. Lack of clinical improvement from 3,4-diaminopyridine in this patient differed from some reports of benefit in animals experimentally poisoned with type A botulinum toxin.

Unrecognized incomplete cervical spinal cord injury: review of nine new and 28 previously reported cases.

Nine patients with unrecognized incomplete cervical spinal cord injury are discussed. Four were sent home as normal, three were called hysterical, and two went undiagnosed during stupor or coma. A literature search revealed 28 additional cases. Eighty percent of these were males, two thirds were over 50 years old, and most had central or posterior cord syndromes. Falls with hyperextension, spondylosis, or disc disease, and motor vehicle accidents were the most common causes. Only one of the 37 had a cervical fracture. In some the neurologic problem was missed altogether; in others it was attributed to hysteria, intoxication, or to other neurologic or systemic diseases. Minor injuries without cervical fracture or dislocation, advanced age, unusual or changeable neurologic deficits, intoxication, and psychiatric problems all contributed to the confusion.

Carpal tunnel syndrome, subclinical median mononeuropathy, and peripheral polyneuropathy: common early complications of chronic peritoneal dialysis and hemodialysis.

Nerve conduction velocity studies were done in median, ulnar, and peroneal nerves, one time each in 46 patients who had been on chronic peritoneal dialysis or hemodialysis for varying lengths of time. Only six patients had normal findings; 37 had peripheral polyneuropathy (15 had isolated polyneuropathy; 22 had median nerve dysfunction in addition); 16 had subclinical median mononeuropathy (14 with polyneuropathy, two without); and nine had overt carpal tunnel syndrome (eight with polyneuropathy, one without). Abnormalities were present in seven of the 11 patients studied after one year of dialysis and in 19 of the 24 patients studied after two years of dialysis. Seventeen patients studied after five years of dialysis all had polyneuropathy. Nine patients studied after seven years of dialysis all had median nerve dysfunction. Abnormalities were as common with peritoneal dialysis as with hemodialysis. Nerve dysfunction was independent of the disease underlying renal failure, the side of the dialysis access shunt, and the presence or absence of osteodystrophy. Dialysis patients need frequent nerve conduction studies from the onset of dialysis to identify carpal tunnel syndrome early and to avoid irreversible nerve damage.

Familial cavernous angioma of the brain stem dominantly inherited in Hispanics.

A 23-year-old Hispanic woman whose mother had died of a brain hemorrhage developed signs and symptoms of a brain stem lesion. These gradually progressed over the next 30 years. Her computed tomographic and magnetic resonance imaging scans show features typical of a cavernous angioma in the brain stem. Her daughter had a transient right hemiparesis at age 25, and at age 28 noted periorbital pain with twitching of the forehead and jaw. The daughter's computed tomographic and magnetic resonance imaging scans likewise suggest cavernous angioma of the brain stem. There has been only one other report of familial cavernous angioma of the brain stem, and that also involved a Hispanic family. Hispanics have a known predisposition to familial cavernous angioma, and this diagnosis should be considered when more than one person in a family develops brain stem symptoms.

Diabetic neuropathy. Structural analysis of nerve hydration by magnetic resonance spectroscopy.

The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated with aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.

Familial cavernous angiomas of the brain in an Hispanic family.

We found cavernous angiomas (CA) in 10 of 22 members of a large Hispanic family. The proband had seizures, and a CA was found at surgery. He and two sisters with seizures had normal angiograms, but CT or MRI showed lesions compatible with CA. Similar abnormalities were found in two cousins with seizures and 5 of 17 asymptomatic relatives studied. MRI proved to be more sensitive than CT for identifying CA. Hispanic families appear to have a predisposition for dominantly inherited CA of the brain.

Atlanto-axial dislocation in acute rheumatic fever. Case report.

A 10-year-old boy had a sore throat, followed in 4 weeks by acute rheumatic fever and in 6 weeks by atlanto-axial dislocation. Reduction of the dislocation by means of a halo vest relieved his pain, but the cervical spine remained unstable after 3 months of immobilization and required an occiput-C1-2 fusion and rib graft to stabilize the atlanto-axial joint. This is the eighth reported case of atlanto-axial dislocation associated with acute rheumatic fever. The features of previous cases are summarized and the clinical aspects, mechanisms, diagnosis, and treatment of atlanto-axial dislocation are reviewed.

Intralabyrinthine osteogenesis in Cogan's syndrome.

Temporal bones from a 64-year-old man who had Cogan's syndrome were examined by light microscopy. Although tissues of the middle ear appeared unremarkable, extensive ectopic bone formation was observed bilaterally in the inner ear membranous labyrinth. Such osteogenesis completely obliterated the cochlear compartments apically. Only the scala tympani compartment of the basal cochlear turn remained patent. Ectopic bone tissue was observed also in the vestibular semicircular canals. Marked degeneration of eighth nerve fibers and associated ganglion cells also was observed. To our knowledge, this report represents only the fourth temporal bone findings of Cogan's syndrome and demonstrates a more advanced pathologic state of inner ear pathology than those reported previously.

Subcortical arteriosclerotic encephalopathy (Binswanger): computerized tomography.

The subcortical arteriosclerotic encephalopathy of Binswanger is characterized clinically by hypertension, dementia, spasticity, syncope, and seizures. It is usually diagnosed pathologically by the finding in white matter of diffuse demyelination or foci of necrosis plus arteriosclerotic and hypertensive vasculopathy. We present a case in which the diagnosis was made on the basis of the clinical course and a computerized tomogram which demonstrated extensive white matter degeneration. Postmortem examination confirmed both the diagnosis and the extent of the degeneration as shown by CT scan.

Familial cavernous angiomas.

Cavernous angiomas are rare, surgically remediable vascular malformations of the CNS that may be characterized by hemorrhage, seizures, or focal neurologic deficits. Three families with cavernous angiomas have been described, and we report two more. In the first, the mother died suddenly with headache. A pontine cavernous angioma was found at autopsy in one son. His brother has similar pontine signs and a radiographically proved pontine mass. The brother's son has seizures and a calcified cerebral lesion. In the second family, the father had a cavernous angioma excised from the caudale. One of the daughters had a hemorrhagic mass removed from the spinal cord. Another daughter has seizures and a temporal lobe vascular lesion proved angiographically. Awareness of the possibility of familial involvement may aid in diagnosis of cavernous angioma.

Neurologic manifestations of Cogan syndrome.

Cogan syndrome is a multisystem inflammatory vascular disease, characterized by nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Recent reports have directed attention to involvement of other organ systems. Respiratory, cardiovascular, gastrointestinal, and musculoskeletal problems are common, as are laboratory abnormalities and general symptoms such as fever, chills, and weight loss. Prominent neurologic problems in two patients prompted a review of 79 cases of Cogan syndrome. More than half had nervous system involvement, including electroencephalographic or spinal fluid abnormality, headache, psychosis, coma, convulsion, neuropathy, and stroke. Cogan syndrome should be considered when neurologic deficits are accompanied by eye, ear, and systemic symptoms.

Abnormal ocular motility with brainstem and cerebellar disorders.

The disorders of ocular motility seen in association with brainstem or cerebellar disorders may point to rather specific anatomical or pathological correlations. Pontine gaze palsy reflects involvement of the pontine paramedian reticular formation. Internuclear ophthalmoplegia signifies a lesion in the medial longitudinal fasciculus. Skew deviation may result from a lesion anywhere in the posterior fossa. Ocular bobbing typically results from a pontine lesion. The Sylvian aqueduct syndrome is characteristic of involvement in the upper midbrain-pretectal region, usually a pinealoma. Cerebellar lesions may be manifested by gaze paresis, skew deviation, disturbances of saccadic or smooth pursuit movements, ocular myoclonus, or several characteristic forms of nystagmus. Familiarity with these disorders may be of great help to the physician dealing with a patient with a possible posterior fossa lesion.