Anna Scalise

Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects

We compared sleep parameters in mentally retarded infantile autism (MRIA) and mentally retarded Downs syndrome (MRDS) by means of polysomnography, evaluating traditional analysis with particular attention to the phasic components in each disorder. Data were compared with those obtained in normal subjects matched for age and sex. Mental age, Intellectual Quotient and the Childhood Autism Rating Scale were performed to obtain an estimation of the neuropsychological deficit. Abnormalities of phasic components of sleep and the presence of REM sleep components into non-REM sleep were observed in both MRIA and MRDS even if in different ways. In fact, MRDS subjects presented a reduction of REM sleep percentage and R index (number of high frequency REMs against number of low frequency REMs) and this was positively correlated to a low IQ. Unlike MRDS subjects, MRIA subjects did not show any parallelism between intellectual abilities and REM sleep deficit. In addition, the presence of undifferentiated sleep in autistic subjects implies a maturational deficit that is still present in adulthood. Finally, a high R index in MRIA was observed. This finding, which is not present in MRDS, could represent an estimation of the disorganized arrival of information caused by a dyscontrol or a reduction of inhibitor pathway. With reference to sleep mechanisms, our results suggest that the cognitive deficit in MRIA may differ from that of MRDS subjects. A maturational deficit of CNS with a dysfunction of brainstem monoaminergic neurons could represent the underlying mechanism.

Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: changes after treatment with controlled-release carbamazepine

Summary: Purpose: To define sleep disturbances in patients with temporal lobe epilepsy (TLE) and explore the association between carbamazepine (CBZ) therapy, sleep, and daytime somnolence.

Pharmacologic reversal of cortical hyperexcitability in patients with ALS

Objective: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission. Background: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness. Methods: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the “drug-free” profile of paired TMS; (2) paired TMS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks’ treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day). Results: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p < 0.01) after diazepam and GBP. Conclusions: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.

Ipsilateral motor activation in patients with cerebral gliomas

Objective: The aim of this study is to provide neurophysiologic evidence of ipsilateral hemispheric activation in patients affected by intracerebral gliomas via the use of transcranial magnetic stimulation. Background: The mechanisms involved in such ipsilateral activation have yet to be established, but they may involve preexisting routes that either are suppressed or undetected in the normal brain. Ipsilateral pathways may act in reserve, activated by the impairment of contralateral control. This hypothesis is suggested by the fact that the considerable size of the tumors in our patients is not matched by a proportionate loss of motor performance in the limbs contralateral to the affected hemisphere. However, it remains possible that ipsilateral motor-evoked potentials (iMEPs) may reflect reorganizational changes without significant functional effects. Methods: The effects of such activation were investigated using both focal and nonfocal coils stimulating cortical motor areas, with MEPs recorded from both left and right thenar muscles. Fifteen healthy control subjects and seven patients were examined. Results: iMEPs were generally absent in normal subjects, but in contrast they were obtained in the patients by stimulating the healthy hemisphere using both round and figure-of-eight coils. Distinct from contralateral MEPs, iMEPs are obtained with higher thresholds (range, 60 to 80% of stimulator output) and display longer latencies (20.9 msec versus 19.4 msec). Conclusions: Taken in conjunction with recent research using functional imaging brain exploration and a variety of clinical, anatomic, and neurophysiologic studies, our results reflect a growing awareness of ipsilateral motor control and its potential compensatory role when contralateral routes are damaged.

Panic disorder or epilepsy? A case report

Psychiatric and neurological disturbances can show up with panic attack symptoms. This report illustrates the difficulty in distinguishing between panic disorder and epilepsy in a subgroup of epileptic patients that suffer panic attacks as symptoms of seizures. This is the first report of panic attacks due to a focal lesion involving the left temporal lobe and the second case of panic attacks related to a meningioma.

Valproate-induced systemic lupus erythematosus in a patient with partial trisomy of chromosome 9 and epilepsy.

Summary: We report a mentally retarded 30–year‐old woman with partial trisomy of chromosome 9 (46,XX6,+der(6)t(6,9)pat) who has had epilepsy since age 11 months. She had been treated with various combinations of drugs. After 1 year of treatment with valproate (VPA) and ethosuximide (ESM), the patient developed arthral‐gias, muscle weakness, fatigue, and fever. Laboratory examination showed increased sedimentation rate, hyper‐gammaglobulinemia, and high titers of antinuclear antibodies (ANA). The possibility of VPA‐induced systemic lupus erythematosus (SLE) was considered. This diagnosis was supported by detection of antihistone antibodies and the HLA‐DR4 antigen. VPA dosage was tapered and discontinued, with accompanying resolution of clinical, immunological and hematological signs of SLE 6 weeks after VPA discontinuation. This is the fourth reported case of VPA‐induced SLE.

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders

OBJECTIVE To investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS). METHODS In basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale-SSS). RESULTS MT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present. CONCLUSION SF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\excitability and\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.

Trisomy 9p and epilepsy

To the Editor: We read the interesting article on Trisomy 9p by J. Stern,1 and want to mention our recent report of a woman with trisomy 9p and epilepsy, similar to the report of Stern, except she had no right-sided choroidal fissure cyst. Our patient had epilepsy from …

Facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy: “Double trouble” overlapping syndrome?

The proband, a white female who was born from nonconsanguineous parents and achieved normal developmental motor milestones, at the age of 45 began to develop progressive weakness involving proximal lower limbs and subsequently the upper girdle muscles (especially on the left side) with difficulties in performing motor tasks such as raising upper limbs or climbing stairs. Blood creatine kinase, routine blood tests and thyroid hormones were within normal limits. Concentric needle electromyography revealed myopathic alterations in the four limbs, in particular in the proximal muscles: polyphasic potentials with short duration, size index below the normative limits of our laboratory and early recruitment were found; active denervation signs were absent [1]. Muscular biopsy was compatible with a slowly evolving myopathy; it showed muscular fibers with different sizes (diameter 24–96 μ), some of them moderately hypertrophic and others moderately hypotrophic; central nuclei were rare (b1%). An immunohistochemical staining for alphasarcoglycan, caveolin-3, trichrome, NADH-TR reductase, COX, SDH, PAS and acid phosphatase did not show significant abnormalities; acid and basic ATPase reaction showed a mild predominance of type I fibers (about 80%). The immunoblot analysis of the dysferlin, dystrophin, alpha sarcoglycan and CAPN3 showed a normal amount of proteins with normal molecular weight. The self-catalytic activity of CAPN3 was normal. A molecular analysis of CAPN3 gene revealed the presence of a heterozygous mutation (c.266A N G, p.Y89C, exon1). During the years the patient also developed facial weakness and the involvement of upper limbs worsened. The patient underwent molecular testing for facioscapulohumeral muscular dystrophy (FSHD) that revealed a D4Z4 deletion, with an EcoRI fragment of 35 kb on chromosome 4q35. The probands daughter presented

A “wavering puff of smoke”: a rare case of moyamoya disease

Dear Editor, Moyamoya disease (MMD) is a rare, idiopathic, chronic, occlusive cerebrovascular disease, characterized by progressive stenosis at the terminal portion of the internal carotid artery associated with abnormal vascular networks in the areas of hypoperfusion. This steno-occlusive pattern is associated with a compensatory development of a collateral network of vessels at the base of the brain, appearing as a Bpuff of smoke^ on conventional angiography (Bmoyamoya^ in Japanese) [1, 2]. There are remarkable regional and racial differences in the frequency of MMD, with mayor prevalence in Korea and Japan compared to the Western Hemisphere. The reasons for this discrepancy remain unknown although recently it has been attributed to the more significant role of MMD genetic susceptibility (genetic variations of RNF213 in the 17q25-ter) in East Asians than in Caucasians [2, 3]. MMD seems affect people of all ages, even if a bimodal distribution with peaks in the first and fourth decades of life is present. In adults, MMD most commonly leads to intraventricular haemorrhage and less frequently to symptoms of ischemia [1, 2]. Cognitive impairment has been documented in MMD. Although it is not severe or generalized in its effects on cognition, MMD appears to affect mental abilities selectively [4]. There is no specific treatment to prevent MMD progression. At present, surgical re-vascularization is the mainstay MMD treatment [5]. Though nature of the ischemic insult in patients withMMD is not an embolic infarction, but instead is mainly a hemodynamic infarct, antiplatelet treatment is usually utilized [5]. In that regard, we would like to present a case of MMD, notably atypical for race, age presentation, clinical manifestations and course. A 57-year-old female with cardiovascular disease and metabolic dysfunctions came to our observation complaining about transient attacks of aphasia, apraxia and mental confusion. Magnetic resonance imaging (MRI) showed multiple ischemic lesions in the context of a chronic vascular encephalopathy. EEG showed abnormal background activity, with abnormalities in the left hemisphere. She started to be treated with antiplatelet medication, but a progressive worsening of symptoms was observed. After 9 months, she had a new cerebral ischemic stroke. MRI showed an acute ischemic lesion in the left hemisphere. One year after our first observation, the patient complained about visual disturbances, a right-sided moderate hemiparesis and a most evident progressive cognitive impairment with languages and attentive deficits. Neurocognitive functions were assessed using standardized neuropsychological tests. Memory, attention, processing speed, verbal memory, visuospatial, language and executive functions were examined. Our patient was found to have pronounced cognitive dysfunction on tests of processing speed, verbal memory, verbal fluency and executive function. The follow-up demonstrated a progressive severe disruption of neurocognition in a broad range of functions, particularly those mediated by subcortical and frontal regions. The pattern of cognitive deficits suggested a mechanism of diffuse small vessel disease most likely due to chronic hypoperfusion related to a hemodynamic, rather than * Anna Scalise annascalise@libero.it