Crespo-Facorro B, Manes F, Plebst C, Morcuende M.  Neuropsychiatric effects of insular stroke. Biological markers of schizophrenic symptoms: functional neuroimaging. Actas luso-españolas de neurología, psiquiatría y ciencias afines 1998

Despite heterogeneous phenotype, lack of pathognomonic symptoms and great variability of symptoms during the course of the illness, functional neuroimaging studies have showed specific patterns of activation associated to particular schizophrenic symptoms or symptom dimensions. Negative symptoms have been associated to hypofrontality; auditory hallucinations seem to be related to abnormalities in brain regions involved in language and, reality distortion dimension has been associated to left temporal lobe impairments.

Manes F, Sergio Paradiso , Springer JA, Lamberty G, Robinson RG.  Neglect after right insular cortex infarction. Stroke 1998 10.1155/2011/514059

Case reports have shown an association between right insular damage and neglect. The aim of this study was to examine the incidence of neglect among patient groups with right or left insular infarction. METHODS: We examined neglect in 9 right-handed subjects with insular stroke as evidenced by CT and/or MRI scans (4 with right insular and 5 with left insular cerebrovascular accident) between 4 and 8 weeks after acute stroke with tests of visual, tactile, and auditory perception. RESULTS: Compared with patients with left insular lesions, patients with right insular lesions showed significant neglect in the tactile, auditory, and visual modalities. CONCLUSIONS: The right insular cortex seems to have a role in awareness of external stimuli, and infarction in this area may lead to neglect in multisensory modalities.

Rabinowicz AL, Salvat J, Leiguarda R, Demonty F, Cervio A, Manes F, Lazarowski A.  Use of antiepileptic drugs in nontraumatic neurosurgical procedures. Is there any best route and time of administration?. Clinical neuropharmacology 1997 10.1097/WNN.0000000000000017

We assessed in 15 consecutive patients the best route and time of administration for phenytoin (PHT) prophylaxis in neurosurgical procedures. We also correlated PHT levels in serum and cerebrospinal fluid after oral and parenteral loading doses. The mean PHT level was 13.9 micrograms/ml in serum and 2.03 micrograms/ml in cerebrospinal fluid (CSF), with a significant correlation between levels in both compartments (r = 0.73, p < 0.01). Mean PHT levels among the different groups were not statistically significant. We conclude that therapeutic levels of PHT in CSF can be achieved independently of the route of administration, as long as accepted loading doses are used.

Ciprian-Ollivier J, Cetkovich M.  Altered consciousness states and endogenous psychoses: a common molecular pathway?. Schizophrenia research 1997

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

Merello M, Starkstein S, Petracca G, Cataneo EA, Manes F, Leiguarda R.  Drug-induced parkinsonism in schizophrenic patients: motor response and psychiatric changes after acute challenge with L-Dopa and apomorphine. Clinical neuropharmacology 1996

Acute single-dose response of drug-induced parkinsonism (DIP) to L-Dopa and apomorphine challenge was evaluated in a double-blind crossover study in 12 schizophrenic patients. There were two noteworthy negative findings. First, neither L-Dopa nor apomorphine produced significant improvements in DIP and second, no changes (neither improvement nor worsening) were found in patients’ psychiatric status. Findings suggest that, for a stimulation dose reaching almost 90% of the responsive dose for idiopathic Parkinson’s disease, no significant changes may reasonably be expected in the parkinsonism of schizophrenic patients treated with neuroleptic drugs.

Starkstein S, Migliorelli R, Manes F, Tesón A, Petracchi M, Chemerinski E, Sabe L, Leiguarda R.  The prevalence and clinical correlates of apathy and irritability in Alzheimer’s disease. The American Journal of Psychiatry 1995 10.3389/fnbeh.2014.00243

We examined the prevalence and correlates of apathy and irritability in a consecutive series of 101 patients with probable Alzheimer’s disease (AD). Based on clinical criteria, 46 (46%) patients had apathy, and 13 (13%) patients had irritability. Apathy was significantly associated with more severe impairments in activities of daily living, significantly more severe extrapyramidal signs, and a significantly higher frequency of both major depression and dysthymia. Patients with irritability had significantly more severe impairments in activities of daily living and significantly higher depression and anosognosia scores. On the other hand, neither apathy nor irritability were significantly associated with deficits in specific cognitive domains.

Starkstein S, Migliorelli R, Tesón A, Petracca G, Chemerinski E, Manes F, Leiguarda R.  Prevalence and clinical correlates of pathological affective display in Alzheimer’s disease. Journal of Neurology, Neurosurgery, and Psychiatry 1995 10.1017/S0033291712000451

This study examined the prevalence and correlates of pathological affect in Alzheimer’s disease. A consecutive series of 103 patients with Alzheimer’s disease were examined with a comprehensive psychiatric assessment that included the pathological laughing and crying scale (PLACS). Forty patients (39%) showed pathological affect: 25% showed crying episodes, and 14% showed laughing or mixed (laughing and crying) episodes. Patients with pathological affect crying showed significantly higher depression scores and a significantly higher frequency of major depression and dysthymia than patients with no pathological affect. Patients with mixed pathological affect showed significantly more subcortical atrophy on CT than patients with pathological affect crying. Forty seven per cent of the patients with pathological affect had no congruent mood disorder, and they showed a significantly longer duration of illness and more severe anosognosia than patients with pathological affect that was congruent with an underlying mood disorder. The study validates the PLACS, and shows the high prevalence of pathological affect in Alzheimer’s disease.

Arévalo GJ, Gershanik O.  Modulatory effect of clozapine on levodopa response in Parkinson’s disease: a preliminary study. Movement Disorders 1993

Clozapine has been shown not only to be effective in ameliorating dopaminomimetic psychosis but to improve parkinsonian symptomatology. Six parkinsonian patients with motor fluctuations under levodopa treatment and severe interdose «off » periods (believed to be mediated by an inhibitory effect of subthreshold levels of levodopa) underwent a trial of clozapine. The effects of this drug on levodopa response were measured by means of an acute levodopa test both before and after receiving clozapine. After 1 month of treatment, clozapine 25 mg/day reduced parkinsonian scores at all stages of the evaluation (pre-levodopa «off, » «on, » and interdose «off «). The effect was consistently more significant for the interdose «off. » Clozapine could be exerting its beneficial effects through the inhibition of an inhibitory effect mediated by low-level dopaminergic stimulation, thus behaving as an apparent anti-parkinsonian drug.

Nogues M, Leiguarda R, Rivero AD, Salvat J, Manes F. Involuntary Movements and Abnormal Spontaneous EMG activity in Syringomyelia and Syringobulbia. Neurology 1999

OBJECTIVE: To describe different types of involuntary movements and abnormal spontaneous electromyographic (EMG) activity in patients with syringomyelia. BACKGROUND: A comprehensive study on involuntary movements in patients with syringomyelia has not yet been undertaken, to these authors’ knowledge. METHODS: One hundred adult patients with syringomyelia were examined over the last 15 years. Involuntary movements were videotaped and evaluated by two independent observers. Electromyographic recordings were made using bipolar surface electrodes. The H-reflex recovery curve was obtained after stimulation of the median nerve at the elbow and recording from the flexor carpi radialis. RESULTS: Involuntary movements or abnormal postures were observed in 22 patients. Three patients showed segmental spinal myoclonus, nine minipolymyoclonus, and four propriospinal myoclonus. Five patients had unilateral or bilateral hand postural tremor (8-10 Hz). Focal or segmental dystonia was observed in three patients. Electromyography showed spontaneous bursts of grouped action potentials synchronous in muscles innervated by the same spinal segment, synchronous firing of neurogenic motor unit potentials, or continuous motor unit activity. Increased H-reflex responses to conditioning stimuli were found in patients with spinal myoclonus. Long latency responses were obtained during peripheral nerve stimulation in four patients. Four patients had rigidity and abnormal upper limb posture. Respiratory synkinesis was observed in three patients. One patient developed inverse masticatory muscle activity. CONCLUSIONS: Patients with syringomyelia showed a wide spectrum of involuntary movements. An increased excitability of spinal motor neurons was probably the basic underlying mechanism.

Manes F, Springer JA, Jorge RE, Robinson RG.  Verbal memory impairment after left insular cortex infarction. Journal of Neurology, Neurosurgery, and Psychiatry 1999

PET studies have shown an association between changes in blood flow in the insular cortex and verbal memory. This study compared verbal memory profiles between a group of four right handed patients with right insular infarction and a group of six right handed patients with left insular infarction. Patient groups were comparable in age, education, and sex. Patients were administered memory tests about 4-8 weeks poststroke. Patients with left insular lesions showed significantly poorer immediate and delayed verbal memory as measured by story A of the WMS-R logical memory I (t=-2.73, p<0.03) and logical memory II (t=-4.1, p<0.004) subtests as well as the CERAD word list memory (delayed recall) (t=-2.4, p<0.05). These findings indicate that left insular damage is associated with poorer performance on verbal memory tasks. The findings suggest that the insula may be part of a functional network that mediates verbal memory.