Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His.

OBJECTIVE: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation. BACKGROUND: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described. METHODS: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient. RESULTS: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member. CONCLUSIONS: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.

Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64.

BACKGROUND: A Canadian family with oculoleptomeningeal amyloidosis with both central and peripheral nervous system disorders was described in 1988. Death of affected family members resulted from recurrent cerebral hemorrhage. OBJECTIVE: To determine if oculoleptomeningeal amyloidosis is caused by a mutation in transthyretin (prealbumin). METHODS: DNA isolated from peripheral blood and archival tissues of affected members of the kindred was studied by direct DNA sequencing and restriction fragment length polymorphism analysis. RESULTS: Direct DNA sequencing identified a thymine-to-cytosine transition at the second base of codon 64, which resulted in a replacement of serine for phenylalanine. This mutation, which creates an additional HinfI site was detected by restriction fragment length polymorphism analysis in each affected individual. CONCLUSION: In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).

Dihydroergotamine and metoclopramide in the treatment of organic headache.

Dihydroergotamine and metoclopramide have been used in the treatment of benign headache for many years. The presumed mechanism of action of dihydroergotamine and metoclopramide is related to these drugs' affinity for serotonergic receptors. We present three cases of the use of dihydroergotamine and metoclopramide in patients with organic headache (two patients with viral meningitis and one patient with meningeal carcinomatosis). All three patients had excellent symptomatic relief. Our results demonstrate that dihydroergotamine and metoclopramide can be effective in treating organic headache and, therefore, symptomatic relief can not be assumed to signify benign disease.

"Top of the basilar artery" syndrome and thalamic aphasia: A case report.

Patients with midbrain infarction are usually comatose and have a poor prognosis. We report a case of "top of the basilar artery" syndrome in an 84-year-old right-handed man with infarction of medial basal thalamus, superior colliculus, pretectal area, medial longitudinal fasciculus, oculomotor nucleus, and left occipital lobe documented by magnetic resonance imaging. The clinical manifestations included right homonymous hemianopsia, bilateral oculomotor palsy, spastic dysarthria, and thalamic aphasia, which correlated with radiological findings. The presentation is unusual because of the extent of involvement in a fairly alert patient with a "pseudo-coma" pattern due to bilateral ptosis and thalamic aphasia.

Using pyridoxine to treat carpal tunnel syndrome. Randomized control trial.

In this study, we examined prospectively the effect of pyridoxine on idiopathic carpal tunnel syndrome. Thirty-two patients with the disease were randomized to receive treatment or placebo. No differences in outcome were found in electrophysiologic signs, clinical signs, or significant symptoms. Our findings do not support the use of pyridoxine for treating carpal tunnel syndrome.

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes presenting without stroke.

OBJECTIVE: To study and describe a large family with the tRNA Leu(UUR) point mutation at position 3243 in mitochondrial DNA, which is associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. DESIGN: Survey; case series. SETTING: University hospital inpatient and outpatient neurology department. PATIENTS: Twelve patients from three generations in a family carrying the tRNA Leu(UUR) point mutation at position 3243 were studied. INTERVENTIONS: Clinical evaluation, muscle biopsy, and mitochondrial DNA point mutation quantitation of the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes in muscle and blood. MAIN OUTCOME MEASURE: Correlation between clinical, pathologic, and genotypic features. RESULTS: Family members had various combinations of sensorineural hearing loss, retinal pigmentary degeneration, migraine, hypothalamic hypogonadism, and mild myopathy. Only one member had a strokelike episode at the age of 46 years. This patient had the highest point mutation percentage. CONCLUSION: This report suggests that this point mutation may not be associated with stroke in all families and that whether patients develop stroke may depend on the percentage of mutant mitochondrial DNA and its tissue distribution.

Anticoagulant therapy and subdural hematoma formation.

Subdural hematoma formation should be considered as a diagnosis in the patient who complains of headache and is on long-term anticoagulant therapy. Three such cases are described and the proper medical management is discussed.

Familial oculoleptomeningeal amyloidosis. Report of a new family with unusual features.

A family had a dominantly inherited amyloid angiopathy that involved the meninges of the brain and spinal cord, retina, vitreous humor, peripheral nerves, and systemic organs. Clinical features included hemiplegic migraine, periodic obtundation, psychosis, seizures, intracerebral hemorrhage, myelopathy, visual impairment, deafness, and peripheral neuropathy. Pathological findings consisted of amyloid deposition in the leptomeningeal and retinal vessels, in the vitreous humor, and in perivascular tissue throughout the body. Evaluation of the amyloid showed it to be a transthyretin (prealbumin). A brief course of plasmapheresis produced a short-lived decrease concentration in circulating transthyretin.

Hemifacial spasm in childhood.

A nine-year-old girl presented with right hemifacial spasm (HFS) of 27 months duration. Stimulation of the right supraorbital nerve produced synkinesis of the ipsilateral facial muscles. Latency and amplitude of the blink reflex were equal bilaterally. Other investigations including computerized tomography (CT) were negative. Treatment with carbamazepine was not helpful. This is the third reported case of HFS in childhood.

Exchange transfusion in neonatal myasthenia gravis.

An infant with transient neonatal myasthenia gravis had a double-blood-volume exchange transfusion because of maternal-fetal blood group incompatibility. This seemed to accelerate both decline in antiacetylcholine antibody titer and clinical improvement.

Changing response to caloric stimulation with gestational age in infants.

Internuclear ophthalmoplegia was found by caloric testing of the vestibuloocular reflex in normal, very premature infants, indicating that the medial longitudinal fasciculus is functionally immature. At this age, the medial longitudinal fasciculus is more responsive to stimulation by the oculocephalic (doll's-eye) reflex, which resulted in conjugate deviation of the eyes.

Unilateral asterixis due to thalamic hemorrhage.

Unilateral asterixis involving the face, hand, and foot was caused by a contralateral hypertensive thalamic hemorrhage, confirmed by computerized tomography. In addition to the asterixis, loss of upward gaze and pupillary abnormalities suggested secondary midbrain compression. These findings raise the possibility that asterixis may be due to mesodiencephalic dysfunction, and suggest that unilateral asterixis can be used to localize focal lesions of this region of the brain.

Familial periodic ataxia.

Two members of a family suffer from recurrent attacks of either vertigo or cerebellar incoordination. The occurrence of these two distinct types of attack in the same patient may reconcile the disparate features of previously reported cases of familial periodic ataxia. The finding of downbeating nystagmus suggests a medullary disturbance. As in a previously reported family, the attacks were relieved by acetazolamide.

Stimulus-induced EEG complexes and motor spasms in subacute sclerosing panencephalitis.

Patients with subacute sclerosing panencephalitis (SSPE) typically present with spontaneous periodic, stereotyped electroencephalographic (EEG) complexes and motor spasms, which are not usually affected by sensory stimuli. This report describes two patients with SSPE in whom the EEG complexes and the motor movements occurred mainly in response to afferent stimuli. Various forms of stimuli were effective in precipitating the movements and EEG complexes, particularly when the stimulus was unexpected or startled the patient. During sleep, the EEG complexes spontaneously occurred in a more periodic fashion, typical of SSPE, but afferent stimuli were still effective in evoking the EEG complexes and associated motor spasms.