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Objective: Seizures in temporal lobe epilepsy (TLE) disturb brain networks and lead to connectivity disturbances. We previously hypothesised that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no studies of ARAS connectivity have been previously reported in patients with epilepsy., Methods: We used resting-state functional MRI recordings in 27 patients with TLE (67% right sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pedunculopontine and ventral tegmental area. Connectivity patterns were related to disease and neuropsychological parameters., Results: In control subjects, regions showing highest connectivity to ARAS structures included limbic structures, thalamus and certain neocortical areas, which is consistent with prior studies of ARAS projections. Overall, ARAS connectivity was significantly lower in patients with TLE than controls (p<0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p<0.01, Pearson's correlation) and was associated with impairments in verbal IQ, attention, executive function, language and visuospatial memory on neuropsychological evaluation (p<0.05, Spearman's rho or Kendell's tau-b)., Conclusions: Recurrent seizures in TLE are associated with disturbances in ARAS connectivity, which are part of the widespread network dysfunction that may be related to neurocognitive problems in this devastating disorder., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To examine prospectively the frequency and nature of psychiatric symptoms seen in patients during the first three months after temporal lobe surgery for chronic intractable epilepsy and in addition to study the relation between presurgical mental state, laterality of surgery, and postsurgical seizure and psychiatric course., Method: A consecutive series of 60 patients being assessed for temporal lobe surgery for intractable epilepsy were studied. They were interviewed before surgery and at six weeks and again at three months after operation., Results: At six weeks after surgery half of those with no psychopathology preoperatively had developed symptoms of anxiety or depression and 45% of all patients were noted to have increased emotional lability. By three months after surgery emotional lability and anxiety symptoms had diminished whereas depressive states tended to persist. Patients with a left hemispheric focus were more likely to experience persisting anxiety., Conclusion: The early months after surgery for epilepsy are characterised by the relatively common presence of psychiatric symptoms. It is proposed that presurgical and early postsurgical neuropsychiatric involvement in programmes of surgery for epilepsy will help to improve the quality of the treatment package offered to patients.

Single photon emission computed tomography (SPECT) with n-isopropyl-p-[123I]iodoamphetamine (IMP) was performed on 20 patients with systemic lupus erythematosus (SLE). Fifteen of the patients showed areas of hypoperfusion. All nine patients who had florid psychiatric manifestations at the time the SPECT was performed had hypoperfusion areas. Four patients who had abnormal SPECT findings during psychiatric remission had psychiatric exacerbation one to six months after the SPECT. Four patients who had no hypoperfusion during psychiatric remission had good psychiatric prognoses. Two patients who had no history of psychiatric abnormality but showed hypoperfusion had psychiatric manifestations one month after the SPECT. The IMP-SPECT may be useful as a biological marker that represents the activity of cerebral involvement underlying psychiatric manifestations and the presence of subclinical CNS involvement.

A 69 year old man with longstanding migraine with aura had four episodes of psychosis lasting 7-28 days during a 17 year period. During attacks he had formed visual hallucination and delusions, including reduplicative paramnesia. His mother was similarly affected. His EEG showed symmetrical frontal delta waves. The time course and EEG changes are similar to acute confusional migraine. The reduplicative paramnesia suggests a focal non-dominant hemisphere dysfunction.

Following a 5 cm left frontal lobectomy for the removal of a mixed astrocytoma-oligodendroglioma, a 51 year old right handed man showed a marked dissociation between his performance on standard neuropsychological tests and his everyday behaviour. In contrast to his intact neuropsychological test performance, he was impaired on a test of "strategy application" which requires goal articulation, plan specification, self-monitoring, and evaluation of outcomes, as well as the establishment of mental "markers" to trigger specific behaviour. Strategy application disorder can therefore be produced by a unilateral circumscribed frontal lobe lesions.

In both animals and humans, Klüver-Bucy syndrome is produced by bilateral temporal lobectomy. It is characterised by hypersexuality, visual agnosia, strong oral tendencies, dietary changes, and hypermetamorphosis. Recurrent, postictal Klüver-Bucy syndrome occurred transiently after seizures in a female who had undergone unilateral temporal lobectomy. The pathophysiological mechanism may have been postictal dysfunction of the remaining temporal lobe, producing a transient functional bilateral temporal lobectomy.

Of 298 patients who had temporal lobectomies for intractable epilepsy, 4 (1.3%) developed post-ictal psychosis for the first time after surgery. All were males of normal intelligence with no pre-operative psychiatric disorder. Psychosis followed both complex partial and generalised seizures. The psychotic symptoms showed polymorphic features. Right temporal lobectomy may increase the susceptibility to post-ictal psychosis in patients who are not seizure free after surgery, particularly in the first post-operative year.

To discover the earliest symptoms and signs of neurological Wilson's disease we analysed the case histories of 136 patients who were seen between 1955-87: patients with hepatic or presymptomatic Wilson's disease were excluded from this series. Thirty one patients (23%) gave a history of an episode of liver damage. The onset of symptoms ranged from nine to 40 years with a median of 16.2 years. The correct diagnosis was made at presentation in only 43 patients. The mean delay before diagnosis was 12.8 months for the others. The earliest symptoms were dysarthria or difficulty with the hands, or often both. There was often an associated change in personality or deteriorating performance at school. The four common clinical pictures were Parkinsonian (61 cases), "pseudosclerotic" (33 cases), dystonic (21 cases) and choreic (15 cases): six cases were unclassified. Parkinsonian symptoms were equally common in children (under 17 years) and adults, a "pseudosclerotic" picture was much more common in adults but dystonic and choreic symptoms were seen more often in children. Experience suggests that no two patients are ever the same, even in a sibship.

Fifty patients who sustained mild to moderate closed head injury (CHI) underwent a CT scan, MRI, and neurobehavioural testing. At baseline 40 patients had intracranial hyperintensities detected by MRI which predominated in the frontal and temporal regions, whereas 10 patients had lesions detected by CT. Neurobehavioural data obtained during the first admission to hospital disclosed no distinctive pattern in subgroups of patients characterised by lesions confined to the frontal, temporal, or frontotemporal regions, whereas all three groups exhibited pervasive deficits in relation to normal control subjects. The size of extraparenchymal lesion was significantly related to the initial Glasgow Coma Scale score, whereas this relation was not present in parenchymal lesions. One and three month follow up MRI findings showed substantial resolution of lesion while neuropsychological data reflected impressive recovery. The follow up data disclosed a trend from pervasive deficits to more specific impairments which were inconsistently related to the site of brain lesion. These results corroborate and extend previous findings, indicating that intracranial lesions detected by MRI are present in most patients hospitalised after mild to moderate CHI. Individual differences in the relation between site of lesion and the pattern of neuropsychological findings, which persist over one to three months after mild to moderate CHI, remain unexplained.

Patients with head injuries frequently complain of a decreased ability to endure intense light and sound stimuli. The few psychophysical studies that have objectively studied this type of hyperaesthesia have not assessed to what extent patients recover from this hyperaesthesia after mild head injury (MHI). A computerised rating technique was used to assess tolerance to intense sound (95 dB) and light (1500 lux) stimuli in patients with an uncomplicated MHI. Patients were tested 10 days and five weeks after the injury. Although most patients substantially recovered from both visual and acoustic hyperaesthesia, 25% of the patients were still not able to endure intense stimuli by five weeks. Analysis of data obtained with two behavioural rating scales (one with post-concussive/cognitive complaints and a second with emotional/vegetative complaints) indicated that visual hyperaesthesia was specifically related to the post-concussive/cognitive complaints scale.

Three patients are described with slowly progressive loss of speech and dysarthria associated with orofacial dyspraxia, initially with intact written language, who subsequently developed more widespread cognitive abnormalities. Positron emission tomography (PET) revealed bifrontal hypometabolism in all of the patients, most marked in the inferior and lateral portions of both frontal lobes, with some extension into the parietal and temporal cortices in one case. These patients may represent a further example of focal progressive cortical degeneration.

Seventeen patients with relapsing remitting multiple sclerosis (MS) and mild physical disability had neuropsychological testing, magnetic resonance imaging (MRI) and single photon emission computerised tomography (SPECT) using technetium 99m (99mTc) hexamethyl-propyleneamine oxime (HMPAO). Performance in verbal fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education matched normal controls. Weighted periventricular and confluent lesion scores and the width of the third ventricle, proved to be the most sensitive MRI measures in differentiating more cognitively impaired patients from those who were relatively unimpaired. Ratios of regional to whole brain activity, measured by SPECT, showed significant reduction in the frontal lobes and in the left temporal lobe of MS patients. A relationship was found between left temporal abnormality in 99mTc-HMPAO uptake and deficit in verbal fluency and verbal memory. Finally, asymmetrical lobar activity indicated a predominant left rather than right temporo-parietal involvement.

To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven's Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting. On the whole, those tasks that seem to require or allow for internal verbalisation resulted in the greatest activation of the left hemisphere compared with the right; right hemisphere activation predominated only in the two tasks primarily involving attention and vigilance. Furthermore, a consistent regional topography of normal cerebral functional laterality was seen: under most conditions left prefrontal cortical activity exceeded that of right prefrontal cortex; during all non-auditory tasks, parieto-occipital cortical activity had an opposite pattern-greater right than left. During most conditions the schizophrenic patients displayed the same pattern. While several cognitively specific between-group differences were found, no single cortical region was consistently implicated and no specific direction of abnormal asymmetry predominated. These data suggest that there is a predominant task-independent functional pattern of cortical activity emphasising relatively greater left anterior and right posterior activation. This pattern may reflect the verbal and attentional primacy of these areas, respectively.

Fifty-three psychiatric patients, 16 with schizophrenia, 19 with affective disorder, and 19 with schizo-affective disorder were diagnosed by Research Diagnostic Criteria. Hoffmann reflex recovery curves were measured in the right and left legs of each patient. In both affective disorder and schizo-affective disorder, recovery curve height in the right and left legs was highly correlated. In schizophrenia, recovery curve height in the right and left legs was not correlated. These results demonstrate a right-left asymmetry in motor neuron excitability specific to schizophrenia. The findings are compatible with a deficit in hemispheric transfer that is unique to schizophrenia. Other interpretations can be made, including diffuse cortical or subcortical dysfunction in schizophrenia which disrupts transfer or interpretation or intrahemispheric communication.

Three deflections or waves of the Contingent Negative Variation (CNV): the Slow Negative Wave (SNW), the Terminal CNV (TCNV) and the Post Imperative Negative Variation (PINV) were studied in 18 adults with Gilles de la Tourette syndrome and in 15 controls. The patients showed a reduced SNW, a normal TCNV and an increased PINV. Moreover, at the right parietal region the patients demonstrated a decreased SNW, TCNV and PINV. The results are discussed in relation to behavioral and neuropsychological disturbances found in Gilles de la Tourette syndrome.

Sporadic reports have suggested central involvement in myasthenia gravis, a disorder in which there is an antibody-mediated loss of peripheral nicotinic acetylcholine receptors. Five patients with symptomatic myasthenia gravis performed an auditory vigilance test of ability to direct and sustain attention, presumed to reflect central cholinergic function. No deficits were found, either in comparison with the same subject's performance when muscle strength had improved after plasma exchange, or compared with that of healthy controls. The results thus failed to substantiate reports of functionally significant central cholinergic deficits in myasthenia gravis.

The habituation index is a quantitative expression of the ability of the orbicularis oculi (blink reflex) to adapt to a series of electrical stimuli applied to the supraorbital region. This parameter has been studied in a group of normal control subjects, and the results compared with those in cases of idiopathic and drug-induced Parkinsonism, states of dementia, and dyskinesias such as Huntington's chorea and senile chorea. Patients with Huntington's chorea showed a tendency for the reflex to habituate readily in contrast to patients with dementia caused by cortical atrophy and those with Parkinson's disease. Younger patients with Huntington's chorea had indices within the normal range. It seems unlikely that this test will prove of value in the detection of clinically unaffected relatives. Where dementia was associated with a reversible intracranial lesion, the habituation index was studied before and after treatment. Failure of habituation in this condition appears to be due to the release of a primitive protective reflex.

The incidence of reduplicative paramnesia was sampled with a structured interview in 50 consecutive alcoholic inpatients. Four had reduplicative paramnesia (RP group) and 46 did not (non-RP group). Three of four patients in RP group had acute right hemispheric lesions and none had a left hemispheric lesion; 19 non-RP patients had left hemispheric lesions, 2 had right, and 25 had none. These data are in keeping with the previous suggestions that the neuroanatomical basis for reduplicative paramnesia is an acute right hemispheric lesion superimposed on chronic diffuse or bifrontal deficit.

Data are presented on four groups using positron tomography and 15 O inhalation. Compared to age-matched volunteer controls, epileptic patients show regions of low blood flow and hypometabolism as found in previous studies. Epileptic psychotic and non-psychotic patients have been compared, and the main differences noted were lower rOER in the psychotic group, especially in frontal, temporal and basal ganglia regions. When a group of psychotic patients receiving neuroleptic drugs was compared to those free of these medications the rOER was higher in the treated sample, and the rCBF fell, significantly in some areas. These data are discussed in the light of other reports of positron tomography in psychosis.

Event-related potentials (ERPs) were recorded from 19 closed head injury (CHI) patients, at least 6 months after injury, and an equal number of control subjects, during a task requiring the covert counting of rare auditory "target" stimuli against a background of frequent "non-targets". In both groups, ERPs to targets contained enhanced frontal N2 and parietal P3 components. N2 was larger in amplitude in the CHI patients than in the controls, and its peak latency was delayed. P3 amplitude was smaller in the patients, but its latency was not significantly different from that of the control group. The delay in N2 latency is interpreted as evidence of an increase in the time needed to achieve stimulus categorisation in CHI patients. The larger N2s in this group are thought to reflect the additional cognitive effort required after CHI to cope with the task. The negative findings with respect to P3 latency suggest that this may be a less sensitive measure of information-processing efficiency in this task than the latency of N2.