Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial.

OBJECTIVES: Peroxisome assembly disorders are genetic disorders characterized by biochemical abnormalities, including low docosahexaenoic acid (DHA). The objective was to assess whether treatment with DHA supplementation would improve biochemical abnormalities, visual function, and growth in affected individuals. METHODS: This was a randomized, double-blind, placebo-controlled trial conducted at a single center. Treatment groups received supplements of DHA (100 mg/kg per day). The primary outcome measures were the change from baseline in the visual function and physical growth during the 1 year follow-up period. RESULTS: Fifty individuals were enrolled and randomized. Two were subsequently excluded from study analysis when it was determined that they had a single enzyme disorder of peroxisomal beta oxidation. Thirty-four returned for follow-up. Nine patients died during the trial of their disorder, and 5 others were lost to follow-up. DHA supplementation was well tolerated. There was no difference in the outcomes between the treated and untreated groups in biochemical function, electroretinogram, or growth. Improvements were seen in both groups in certain individuals. CONCLUSIONS: DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders. CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence that DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders during an average of 1 year of follow-up in patients aged 1 to 144 months.

Cognitive and brain magnetic resonance imaging findings in adrenomyeloneuropathy.

Neuropsychological functioning and brain magnetic resonance imaging (MRI) were evaluated in 84 men with adrenomyeloneuropathy (AMN). MRI was normal in 61%, the "pure AMN" group, while 39%, the "cerebral AMN" group, showed brain white matter abnormalities. Except for mild deficits in psychomotor speed and visual memory, neuropsychological function was normal in pure AMN. Most patients with cerebral AMN had normal IQ and language but evidenced impaired psychomotor speed, spatial cognition, memory, and executive functions. Patients with MRI evidence of very severe cerebral disease had global and language impairment as well, and deficits in all patients were highly correlated with degree of brain MRI involvement.

Disruption of automatic speech following a right basal ganglia lesion.

Following a right basal ganglia lesion, a right-handed man, age 75, was unable to recite familiar verses. Serial automatic speech, singing, recitation of rhymes, and swearing were impaired, and only idioms and social greetings were preserved. Speech no longer contained overused phrases and he could comprehend automatic speech. In contrast, propositional speech was preserved in both French and Hebrew. Right basal ganglia lesions may impair production but not comprehension of automatic speech.

Comprehension of prosody in Huntington's disease.

Patients with Huntington's Disease (HD) who were without dementia were compared to unilateral stroke patients and controls as previously reported in 1983, to discover if they had a prosodic defect. Subjects were presented tape-recorded speech filtered sentences and asked to indicate the tone of voice as happy, sad or angry (affective prosody), or as a question, command or statement (propositional prosody). HD patients were impaired in comprehension of both types of prosody compared to controls but were not different from stroke patients. A second study compared early HD patients with at-risk siblings and spouse controls on comprehension of affective and propositional prosody, discrimination of both types of prosody, rhythm discrimination and tonal memory (Seashore tests). HD patients were impaired in both comprehension and discrimination of all types of prosody. HD patients were less accurate than at-risk patients on the tonal memory task but not on the rhythm discrimination task. These findings suggest compromise in ability to understand the more subtle prosodic aspects of communication which may contribute to social impairment of HD patients very early in the course of the disease.

Cognitive impairment in adult-onset adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a progressive X-linked disorder that produces pathological changes, mainly in the adrenal cortex and the white matter of the central nervous system. The main biochemical abnormality is the accumulation of saturated unbranched fatty acids with a chain length of 24 or more, referred to as very-long-chain fatty acids (VLCFA). Affected children develop large zones of demyelination associated with perivascular lymphoctyic infiltrations resembling those seen in multiple sclerosis. Adults show a more chronic form of the disease, referred to as adrenomyeloneuropathy (AMN). AMN mainly involves the spinal cord ad peripheral nerves, although the cerebral hemispheres may also be affected. Approximately 15% of female carriers have nervous-system involvement that resembles AMN. It is well known that ALD may initially appear as a psychiatric disorder. In the present study, we have assessed the prevalence of cognitive impairment in a group of AMN patients and neurologically symptomatic ALD heterozygotes initially presenting primarily physical complaints. Sixty percent of these patients demonstrated significant neuropsychological impairment, most commonly a pattern of spared and impaired functions typical of a subcortical dementia. We suggest that this progressive cognitive impairment may underlie other behavioral deficits, affirming the significance of the psychological features of this genetically determined disorder.

Confrontation naming deficit in dementia of depression.

Unlike patients with irreversible dementia, elderly depressed patients with cognitive impairment are thought to have relatively preserved recognition, memory, and language abilities. To test this hypothesis, the authors compared memory and naming performance in elderly hospitalized patients with major depression alone, reversible dementia of depression, or irreversible dementia. All patient groups performed worse than nondemented, nondepressed control subjects on memory tasks. Patients with dementia of depression performed worse than depressed patients with normal cognition on tests of free recall, delayed recall, and verbal delayed memory but not on tests of delayed visual memory. Patients with dementia of depression and patients with irreversible dementia were severely compromised in both speed and accuracy on the confrontation naming task.

Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia').

Twenty-six elderly (greater than 60 yrs) patients with DSM-III major depression were compared to 13 patients with NINCDS/ADRDA probable Alzheimer's disease (AD), and to 31 screened normal controls. Subjects were matched on age and sex. Fifteen of the 26 depressed patients were cognitively impaired on the Mini-Mental State Examination (MMSE) upon admission, but after treatment returned to the normal range. These 15 patients were defined as having the dementia syndrome of depression (DOD). The remaining 11 depressed patients were termed depressed, cognitively normal (DCN). All subjects received standardized cranial CT scans for assessment of ventricular brain ratio (VBR) and CT attenuation numbers. Subjects also received neuropsychological evaluation. CT values for the 26 depressed patients lay between those of AD patients and normal controls. CT values for the DOD subgroup clustered near those of AD patients. Patterns of cognitive deficits and correlations of CT attenuation values with cognitive measures were also similar in AD and DOD. Most patients were reassessed at a mean of two years after initial testing; of the 11 of the 15 DOD re-examined, only one had undergone cognitive decline. By contrast, all AD patients retested had declined significantly. Episodes of DOD and DCN tended to 'breed true'. This study suggests that while patients with DOD may have underlying structural brain abnormalities, obvious short-term progression to AD does not commonly occur.

Olfactory recognition: differential impairments in early and late Huntington's and Alzheimer's diseases.

Forty-two patients with senile dementia of the Alzheimer type (SDAT), 38 patients with Huntington's disease (HD) and matched normal controls were administered tests of olfactory, verbal, and visual recognition after being screened for normal olfactory discrimination. Early-affected Huntington's patients (EHD) with minimal chorea or cognitive deficit displayed marked deficits in olfactory recognition despite normal verbal and visual performance, even after correction for task difficulty, suggesting involvement of olfactory brain regions early in the disease process. In the early Alzheimer's group (EAD), marked deficits were seen on all recognition modalities indicating more global impairment. Both overall (early plus late) patient groups were impaired relative to controls on all recognition tasks, with the olfactory paradigm being most affected.

Comparison of two intravenous sedation techniques for percutaneous radio frequency trigeminal rhizotomy. A pilot study.

Conscious sedation, as used in dentistry and oral surgery, has been used satisfactorily to manage patients undergoing the intense pain encountered in radio frequency trigeminal rhizotomy for tic douloureux. The pain produced by this procedure cannot be blocked by local anesthesia. General anesthesia cannot be used because of the need for sensory testing in an awake, cooperative patient. Conscious sedation using alphaprodine, hydroxyzine, methohexital, and intensive behavioral modification was compared with a neuroleptic intravenous sedation technique using droperidol, fentanyl, and thiopental. Patients managed with conscious sedation were found to be more amnestic for the pain of surgery, a difference that persisted six months later.

Conscious sedation for minor gynecologic surgery in the ambulatory patient. A pilot study.

A conscious sedation regimen consisting of alphaprodine, hydroxyzine, and methohexital together with intensive behavior modification was evaluated in an open pilot study for patients undergoing minor gynecologic surgery. This combination was found to result in hemodynamic stability, satisfactory patient compliance, and patient and surgeon acceptance. Patients were unable to recognize words taught to them just after drugs were administered.Electroencephalogram (EEG) changes seen in general anesthesia or deep sedation were not found in the EEG records of a subset of patients. These findings suggest that conscious sedation can provide adequate relief of pain and anxiety for minor gynecologic procedures when local anesthesia can achieve only partial pain relief.

Comprehension of emotional prosody following unilateral hemispheric lesions: processing defect versus distraction defect.

Two studies were conducted in order to determine whether the poor performance of RHD patients on emotional prosody tasks could be attributed to a defect in perceiving/categorizing emotional prosody (processing defect) or to a problem in being distracted by the semantic content of affectively intoned sentences (distraction defect). In one study, patients with RHD, LHD or NHD listened to affectively intoned sentences in which the semantic content was congruent or incongruent with the emotional prosody. In a second study, the patients listened to affectively intoned sentences that had been speech filtered or unfiltered. Findings from these studies indicate that both processing and distraction defects are present in RHD patients.

Phonologic agraphia in a left-handed patient after a right-hemisphere lesion.

Oral and written spelling were evaluated in a left-handed patient with a right-hemisphere infarct and right-hemisphere language representation. Spelling was intact for different classes of words, but there was severe difficulty in both oral and written spelling of nonwords. This pattern was consistent with phonologic agraphia. There was selective disruption of the segmentation component, with intact phoneme-to-grapheme conversion supporting the Roeltgen and Heilman hypothesis of two-system spelling after lesions in the left supramarginal gyrus. This is the first case of phonologic agraphia after right supramarginal gyrus damage in a left-handed patient.

Comprehension of affective and nonaffective prosody.

We studied patients with damage of either the right (RHD) or left hemisphere (LHD) and control subjects to determine whether the RHD patients had a global or limited prosodic defect. Compared with LHD patients and controls, RHD subjects had decreased comprehension of emotional prosody. Both LHD and RHD groups had more impaired comprehension of propositional prosody than controls, but the RHD and LHD groups did not differ. The right hemisphere, therefore, seems to be dominant for comprehending emotional prosody but not propositional prosody.

Repetition of affective prosody in mixed transcortical aphasia.

Two patients with mixed transcortical aphasia could repeat propositional speech but not affective prosody. These findings suggest that the intact perisylvian region responsible for propositional speech does not mediate effective prosody. We propose that affective prosody is incorporated into propositional speech by means of an interhemispheric mechanism and that the failure of these patients to repeat affective prosody was caused by a disconnection of the left perisylvian structures from the right hemisphere structures thought to mediate affective prosody.

Anterograde memory deficits for visuospatial material after infarction of the right thalamus.

A patient with a discrete lesion in the region of the right dorsomedial thalamic nucleus had anterograde memory impairment for visuospatial material. The thalamus may be critical for memory function because of its reciprocal connections with dorsolateral and orbitofrontal cortex and also because of its participation in both basolateral and medial limbic systems.

Amnestic disturbance following infarction of the left dorsomedial nucleus of the thalamus.

A patient with a discrete lesion in the region of the left dorsomedial nucleus of thalamus had anterograde memory impairment for verbal material.