Roberto Gallassi

Cognitive impairment in motor neuron disease.

ABSTRACT – A systematic investigation of the cognitive functions of 22 patients affected with motor neuron disease (MND) compared to 36 controls matched for age and education was performed. The MND group showed cognitive performances slightly but significantly lower than the control group; 6 MND patients, however, had decidedly pathological values. Cognitive impairment was stereotyped and global, with sparing of memory. There was no significant difference between patients with isolated involvement of the lower motor neuron and those with associated pyramidal involvement. Our neuropsychological findings are in agreement with previous clinical, neuroradiological and pathological reports indicating extra‐motor cerebral involvement in MND.

Clinical Features of Fatal Familial Insomnia: Phenotypic Variability in Relation to a Polymorphism at Codon 129 of the Prion Protein Gene

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake‐sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio‐dorsal and anterior‐ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1+ 1.1 months) or a prolonged (30.8 + 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mai seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein‐gene.

[18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.

We used [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypo-metabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.

Neuropsychological, electroencephalogram and brain computed tomography findings in motor neuron disease.

Thirty-five patients affected with sporadic motor neuron disease (MND) and without clinically evident mental deterioration were systematically investigated by means of neuropsychological tests, quantitative analysis of EEG and brain CT. The MND patients as a group showed a slight but definite and stereotyped cognitive impairment. Temporal slow EEG activity was increased in the whole MND group and posterior background activity was slower in the more cognitively impaired patients. No significant differences were found in CT measurements of brain atrophy between MND and controls.

Melanopsin retinal ganglion cell loss in Alzheimer disease

Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.

Epileptic Amnesic Syndrome: An Update and Further Considerations

Summary:  We describe 30 patients with “epileptic amnesic syndrome” (EAS) with adult‐senile onset of a severe memory complaint that started before or at the same time as stereotyped seizures with only short loss of contact and automatisms. Because the seizures were not obvious or disturbing, they remained undiagnosed for a long time. Twenty‐three patients also had attacks of transient anteroretrograde amnesia after the seizures: “epileptic amnesic attacks” (EAA). These are similar to attacks of transient global amnesia but are more frequent, shorter, accompanied by clear‐cut clinical epileptic manifestations, and respond favorably to antiepileptic drug (AED) therapy. Interictal neuropsychological investigation ruled out global mental deterioration, showing only selective memory impairment in a few long‐term tasks, and subjective and objective improvement after AED. Bilateral deep discharges involving the hippocampal‐mesial temporal lobe regions may explain EAA, which is probably a postictal phenomenon. The interictal memory problems may be due to subclinical discharges causing difficulty in codification or consolidation of the amnesic trace. EAS patients having uniform anamnestic, clinical and neuropsychological features represent a particular type of temporal lobe epilepsy. We propose a definition of EAS, according to which cases can be classified as definite, probable or possible forms.

Fatal familial insomnia Behavioral and cognitive features

Fatal familial insomnia (FFI) is a familial prion disease linked to a mutation of the prion protein gene.Neuropsychological investigations in seven patients with FFI belonging to two different families showed that the main behavioral and neuropsychological features are (1) early impairment of attention and vigilance, (2) memory deficits, mainly of the working memory, (3) impairment of temporal ordering of events, and (4) a progressive dream-like state with neuropsychological and behavioral features of a confusional state. Neuropathologic examination of six patients showed prominent neuronal loss and gliosis involving the anterior ventral and mediodorsal thalamic nuclei, with additional cerebral cortical involvement in two cases. Clinicopathologic correlations indicate that FFI is associated with a neuropsychological and behavioral syndrome that is distinct from the cortical and subcortical dementias, and Wernicke-Korsakoff syndrome. These findings offer insights into the function of the thalamic nuclei and challenge the notion of thalamic dementia. NEUROLOGY 1996;46: 935-939

Epilepsy presenting as memory disturbances.

Summary: Six patients presented with severe adult‐onset memory deficit that was subsequently diagnosed as complex partial epilepsy. In three cases acute amnestic episodes also occurred. The seizures were characterized by short losses of contact and oral automatisms. Interictal EEG showed temporal abnormalities of varying degrees. Formal neuropsychological assessment revealed dissociation between the subjective complaint and the test performances that showed a selective impairment in a few long‐term verbal memory tests. These patients present a characteristic clinical picture of memory disturbance as the prominent feature of partial seizures.

Cognitive effects of valproate

The effects of valproate on cognition are usually considered to be minimal, but few formal neuropsychological studies are available. We studied the psychomotor performances of 20 seizure-free epileptics during fixed valproate monotherapy and after its withdrawal. Our findings suggest some adverse effects of valproate which appear to be completely reversible after withdrawal.

Are subjective cognitive complaints a risk factor for dementia

The objective is to evaluate the prognosis of subjective cognitive complaints (SCC) patients during 4-year follow-up. A prospective study on 92 SCC patients investigating their cognitive, affective and behavioural aspects. SCC patients were classified as having no objective cognitive impairment (NOCI), mild cognitive impairment (MCI), or subtypes of MCI. Results: 43 patients were found to have NOCI and 49 MCI. During the follow-up, 45.5% of NOCI patients remained unchanged, 13.9% were diagnosed as MCI and only one progressed to dementia. Of the MCI patients, 32.3% remained stable, 18.4% became demented and 4% reverted to NOCI. Visual attention, behavioural memory, long-term verbal memory, apathy and caregiver distress, provided independent predictors of progression to dementia.