Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.

A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.

Adherence of Candida species to human epidermal corneocytes and buccal mucosal cells: correlation with cutaneous pathogenicity.

Adherence of microorganisms to epidermal corneocytes may be a prerequisite for cutaneous colonization and infection. Six species of Candida were assayed in vitro for adherence to human epidermal corneocytes and buccal mucosal cells, and compared to previous studies of pathogenicity in a rodent model of cutaneous candidiasis. C. albicans and C. stellatoidea exhibited marked adherence to both epithelial cell types over time, and were cutaneous pathogens in the rodent model. The remaining species showed little or no adherence, and were nonpathogenic to skin. Adherence to corneocytes was not inhibited by ethylenediamine tetraacetic acid, mannan polysaccharide, or concanavalin A lectin. Fresh human serum, but not heat-inactivated serum, inhibited C. albicans adherence by 50%, and was associated with the deposition of complement components, C3 and factor B on blastospores. Adherence to epithelial corneocytes and mucosal cells is a property of pathogenic species of Candida, and may participate in cutaneous colonization and infection mechanisms. Adherence was time-dependent, and did not require divalent cations. Cell wall mannan may participate in the "adhesin" complex. Mannan activation of serum complement and deposition of C3 and factor B on blastospores may provide a protective action by inhibiting Candida adherence to corneocytes.

Opsoclonus in adults. Report of three cases and review of the literature.

Opsoclonus is a rare but distinctive disorder of ocular motility. Although there are many reported cases of opsoclonus in children, there is no large series of cases in adults. In recent years, three cases of opsoclonus in adults have been identified at the University of Iowa, Iowa City. Review of 55 other cases of opsoclonus in adults reported in the literature showed that adults over 40 years of age with onset of opsoclonus should be investigated fully for underlying malignancy. In younger adults with a history of a preceding influenzalike illness, viral titers (acute and convalescent) should be obtained. Also, younger adults should be investigated for other causes of opsoclonus, such as drug or toxin exposure. Treatment is directed toward correcting the underlying process.

Pseudotumor cerebri in men.

We describe 29 men with pseudotumor cerebri (PTC) and compare them with aged-matched women with PTC and male control subjects. Pseudotumor cerebri occurs less frequently in men but in a similar age distribution. Although signs and symptoms of PTC are similar in men and women, men may require surgical treatment for impending visual loss. Black men appear to be at greater risk to loss of vision. Even though men with PTC are less likely to be obese than women, they tend to be more obese than control subjects and should be counseled on weight-reduction diets.

Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia.

OBJECTIVE: This study was undertaken to evaluate the hypothesis that severe preeclampsia and eclampsia are associated with unique cranial magnetic resonance images. DESIGN: Case series of women with severe preeclampsia and eclampsia. SETTING: Referral center. PATIENTS: Sixteen women with severe preeclampsia and 10 women with eclampsia. RESULTS: Half of the women with severe preeclampsia had abnormal scans with nonspecific foci of increased signal in the deep cerebral white matter on T2-weighted images. However, women with eclampsia had either a multifocal area of increased signal at the gray-white matter junction on T2-weighted images or cortical edema and hemorrhage. These findings are consistent with necropsy descriptions of cortical edema and petechial hemorrhage. Basal ganglion lesions were also common. CONCLUSIONS: These findings appear to be unique to eclamptic women and should be considered of diagnostic significance in contrast to the nonspecific changes in patients with severe preeclampsia. Cranial magnetic resonance imaging may, thus, be of value in cases with diagnostic uncertainty, atypical presentation, or focal neurologic deficit.

Thrombosis of the deep venous drainage of the brain in adults. Analysis of seven cases with review of the literature.

OBJECTIVES: To characterize the clinical, radiographic, and pathologic findings in thrombosis of the deep venous drainage of the brain. To highlight clinical and radiographic findings that may lead to the diagnosis of disease and distinguish it from dural sinus thrombosis. To review the published literature on this disorder. DESIGN: Retrospective review of the medical and radiographic records of seven patients from three institutions over the past 10 years. Review of the English language literature from 1971 to the present. RESULTS: All seven patients had risk factors for cerebral venous thrombosis. Five patients presented with a short, rapidly progressing course characterized by headache, nausea and vomiting, and decline in level of consciousness. All five patients died or were rendered severely disabled. Computed tomographic scans, magnetic resonance imaging, and magnetic resonance angiography showed findings associated with deep cerebral vein thrombosis in three of four, in five of five, and in three of three patients, respectively. Transfemoral catheter angiography was diagnostic in two of two patients. Twenty-one reported cases of deep cerebral venous thrombosis were identified in the literature. CONCLUSIONS: When the two populations are combined and compared with large series of patients with dural sinus thrombosis, patients with deep venous system thrombosis are more commonly women, tend to present with a more rapidly declining time course, altered consciousness, and long tract signs. Death or long-term sequelae are far more likely to occur in internal cerebral vein thrombosis than with dural sinus thrombosis. Unenhanced computed tomography can demonstrate findings that are strongly suggestive of the diagnosis. Magnetic resonance imaging and magnetic resonance angiography are confirmatory. Angiography may still be necessary when the diagnosis is not clear.

Psychogenic respiratory distress.

Five patients developed recurrent episodes of psychogenic respiratory difficulty that were superimposed on psychogenic neurologic symptoms. Misdiagnosis resulted in long hospital stays, code blue alerts, intubation, mechanical ventilation, and, in one case, tracheostomy. Patients "learned" psychogenic respiratory distress because their breathing symptoms evoked distinct evidence of anxiety in physicians and staff. In these patients, gain was not incidental but exerted primary control over symptom selection. The behavioral mechanisms involved in the pathogenesis of psychogenic respiratory distress have significant implications for its diagnosis, treatment, and prevention.

Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review.

Fraternal twin sisters developed idiopathic intracranial hypertension (IIH) shortly after beginning tetracycline for treatment of acne. We reviewed from the literature 19 familial cases of IIH and 37 cases of IIH associated with tetracycline usage. Among the 37 combined adult and pediatric cases, 26 of 37 had resolution of signs or symptoms of IIH within hours to days of stopping the antibiotic, and rapid recurrence with reinitiation of drug occurred in 4 of 37. We suggest that these cases may be tetracycline-induced, may be related to an underlying genetic susceptibility, and support the notion of multifactorial etiologies for IIH.

Idiopathic intracranial hypertension: relationship to depression, anxiety, and quality of life.

OBJECTIVE: To explore the incidence of depression and anxiety and to measure quality of life in women with idiopathic intracranial hypertension (IIH), a matched group cross-sectional study was conducted. Women with IIH (n = 28) were compared with control groups of weight- and age-matched women not diagnosed with IIH (n = 30) and with age-matched women of normal weight (n = 30). METHODS: Eighty-eight women completed a questionnaire soliciting health information and standardized questionnaires measuring depression, anxiety, and quality of life. The groups were compared using analysis of variance and chi2 tests. Where appropriate, post hoc comparisons were made using Fisher's test. RESULTS: Patients with IIH reported a greater number of adverse health problems than either of the control groups. Non-health-related psychosocial concerns were equally prevalent among the three groups, but IIH patients were significantly more affected by hardships associated with health problems than the other two groups. The patient group also had higher levels of depression and anxiety than the control groups. These adverse health conditions were reflected in decreased quality of life measures for the IIH patients. CONCLUSIONS: This study supports previous reports that link obesity and psychosocial difficulties, but obesity alone is not the explanation for the higher levels of depression and lower levels of quality of life.

CT and hemifacial spasm.

Forty-six patients with typical hemifacial spasm had CT. Thirty-eight (83%) were abnormal, including two with surgically documented tumors. Thirty-six had a characteristic dolichoectatic vertebrobasilar artery, with the convexity pointing to the side of the spasm in 92% of the scans. This study suggests that CT is worthwhile procedure in the evaluation of hemifacial spasm and that dolichoectatic vertebrobasilar arteries are very frequently associated with hemifacial spasm.

Pseudotumor cerebri and pregnancy.

Pseudotumor cerebri (PTC) is most commonly seen in obese women of reproductive age. We studied 109 women with PTC between ages 16 and 44 years. In 11, PTC started during pregnancy. Thirteen women with previous diagnosis of PTC, including two of the aforementioned 11, had an additional 17 documented pregnancies. Patients were matched by age and parity with controls. Obstetric complications occurred more frequently in the controls. Visual loss occurred with the same frequency in pregnant and nonpregnant patients. Treatment of PTC patients in pregnancy should be the same as for nonpregnant PTC patients, except that calorie restriction and diuretic use are contraindicated. Obstetric management is no different from that of normal pregnancy.

Autosomal dominant cerebellar ataxia with retinal degeneration: clinical, neuropathologic, and genetic analysis of a large kindred.

The autosomal dominant cerebellar ataxias (ADCA) comprise a heterogeneous group of neurologic disorders characterized by degeneration of the cerebellum, spinal cord, and brainstem. Genetic analysis has revealed two loci, SCA1 on chromosome 6p, and SCA2 on chromosome 12q, responsible for some ADCA. We present a four-generation kindred of 42 individuals, 12 of whom were clinically affected with ADCA and an associated cone dystrophy. Early loss of color discrimination with retinal and macular signs is followed by gradual progression of cerebellar dysfunction and development of pyramidal signs. Pathology shows degeneration of cerebellum, basis pontis, inferior olive, and retinal ganglion cells. For genetic analysis, we used polymorphic markers D6S89 and D12S79; linkage analysis gave negative results, excluding linkage to both SCA1 and SCA2. The data strongly support genetic heterogeneity consistent with the unique clinicopathologic features of the form of ADCA displayed in this large family.

Serum vitamin A concentration is elevated in idiopathic intracranial hypertension.

OBJECTIVE: The primary purpose was to investigate whether serum vitamin A concentration is associated with idiopathic intracranial hypertension (IIH). The secondary aim was to obtain pilot data regarding the amount of vitamin A ingested by patients and controls. BACKGROUND: Vitamin A is an attractive candidate mediator of IIH as many of the symptoms and signs of hypervitaminosis A mimic those of IIH. METHODS: We prospectively determined serum retinol and retinyl ester concentration in 16 women with IIH and 70 healthy young women. Using a survey instrument, we also determined the average daily vitamin A ingestion in a convenience sample of patients and controls. RESULTS: Serum retinol concentration was significantly higher in the patient group (median 752 ug/L) compared with the control group (median 530 ug/L), even after adjusting for age and body mass index (p < 0.001). Retinyl ester concentration, however, was similar in the patient (median 48 ug/L) and control (median 41 ug/L) groups (p = 0.32). There was no significant correlation between serum retinol concentration and body mass index in the patients (r = 0.16) or controls (r = -0.02). Finally, there was no significant difference in the amounts of vitamin A ingested by the patients or controls, although the small number of subjects in both groups reduced the power of this conclusion. CONCLUSIONS: Elevated serum retinol concentration is associated with IIH. Obesity, by itself, does not explain these higher levels. Patients may ingest an abnormally large amount of vitamin A, metabolize it abnormally, or be unusually sensitive to its effects. Alternatively, elevated level of serum retinol may reflect an epiphenomenon of another variable we did not measure or a nonspecific effect of elevated retinol binding capacity.

Central neurogenic hyperventilation: pharmacologic intervention with morphine sulfate and correlative analysis of respiratory, sleep, and ocular motor dysfunction.

Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH.

Cranial magnetic resonance imaging in eclampsia.

Although the precise neuropathologic basis for eclamptic convulsions remains unclear, intracranial hemorrhage is frequently associated with fatal cases. Magnetic resonance imaging (MRI) is a recently developed neuroimaging technique that appears superior to other processes for defining intracranial anatomy and pathophysiology. This technique has not yet been reported in eclampsia. The authors performed serial MRIs on an eclamptic woman, with findings compatible with previously described neuropathologic changes.

The association of antiphospholipid antibodies with severe preeclampsia.

Over a 3-year period, we studied 43 women who presented with severe preeclampsia prior to 34 weeks' gestation. Seven (16%) had significant levels of antiphospholipid antibodies, whereas none of the normotensive controls of similar gestational age had antiphospholipid antibodies (P less than .001). Three of the seven women with antiphospholipid antibodies suffered the following complications during the peripartum period: 1) cerebral infarction and episodes of transient monocular blindness; 2) pulmonary embolism, deep venous thrombosis, and an autoimmune flare in the postpartum period; and 3) transient monocular blindness and amnesia after delivery. Our experience suggests that antiphospholipid antibodies are found in a substantial proportion of cases of early-onset severe preeclampsia and have important clinical implications. We suggest that patients with early-onset severe preeclampsia be screened for antiphospholipid antibodies; if antibodies are detected, these women should be considered for prophylactic anticoagulation therapy.

Pupillary constriction during forceful eyelid closure.

Pupillary constriction during forceful eyelid closure was investigated in 30 normal subjects. The right eye of each subject was filmed with an infrared-sensitive television camera in darkness before, during, and after eyelid closure. Clinically detectable constrictions were found in nine of the 30 subjects (30%). No significant correlation was found between amplitude of constriction and age of subject or baseline pupillary diameter. Forceful eyelid closure should be considered as a technique to elicit pupillary constriction in patients with a poor near response, but many subjects will have no detectable constriction using this maneuver.

Retinal toxicity associated with occupational exposure to the fish anesthetic MS-222.

PURPOSE: To report a case of retinopathy associated with chronic occupational exposure to ethyl-m-aminobenzoic acid methanesulfonate (MS-222), a retinotoxic fish anesthetic. METHOD: Case report with electroretinograms to document changes in visual electrophysiology. RESULTS: An ichthyologist with a long history of skin exposure to MS-222 was initially examined for decreased vision, photophobia, and photopsia. His electroretinogram abnormalities were similar to those seen in animal models of acute MS-222 toxicity. After terminating MS-222 contact for 7 months, his vision returned to normal, and his electroretinogram improved. CONCLUSION: Individuals with occupational exposure to MS-222 should exercise caution to avoid systemic absorption of this retinotoxic compound.

Acquired and progressive retinal nerve fiber layer myelination in an adolescent.

PURPOSE: To report the onset and progression of retinal nerve fiber layer myelination in an adolescent patient. METHODS: Case report. RESULTS: A 7-year-old male was found to have myelination of the retinal nerve fiber layer in the left eye. When he was reexamined at age 14 years, he was found to have new myelination in the right eye, progression of the myelination in the left eye, and bilateral optic nerve drusen. CONCLUSION: Retinal nerve fiber layer myelination can occur spontaneously in adolescence, progress in adolescence, and be associated with optic nerve drusen.

Maternal orbital hematoma associated with labor.

We examined two women with orbital hematomas that occurred during labor. Both women developed sudden diplopia, proptosis, and orbital pain. The location of the hematoma was confirmed by orbital echography and computed tomography. The patients were observed without surgical intervention. Neither patient developed clinical or echographic signs of compressive optic neuropathy. Clinical resolution occurred during the following two weeks. Serial standardized orbital echographic examinations documented resolution of the hematomas.