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Biomedical subjects

J Ghika

Publications and source records attributed to J Ghika.

At least 55 records · Page 3Linked to original sources
PubMed1997

Clinical efficacy and tolerability of a new levodopa/benserazide dual-release formulation in parkinsonian patients. L-Dopa Dual-Release Study Group.

To improve the response of parkinsonian patients to L-Dopa treatment, a new preparation of L-Dopa/benserazide with dual-release properties was developed. The breakable three-layer tablets with biphasic dissolution kinetics combine the advantages of the standard and sustained-release formulations. The clinical efficacy of this new formulation was assessed in an open-label, pilot study for 14 weeks conducted by Swiss neurologists. Sixty-one parkinsonian patients were included: 5 (8%) patients were de novo, 39 (64%) had fluctuations, and 17 (28%) without fluctuations. The mean Hoehn and Yahr stage was 2.6 and the mean duration of disease was 7.4 years. The best prestudy treatment was kept stable for 2 weeks before entering the first 8-week period in which standard and/or sustained L-Dopa treatment could be either entirely or partially substituted by the dual-release formulation, which was as far as possible kept unchanged during the second 6-week period. During the substitution period, the overall dose of L-Dopa was significantly increased by 11.5%, probably reflecting some differences in the bioavailability of the various galenical formulations, and the mean daily drug intakes were reduced from 5.4 at baseline to 4.1 at week 8 (a 24% reduction, p < 0.001). Sixteen percent of the patients dropped out of the study because of unsatisfactory results, but none left for safety reasons. At the end of the study, complete substitution was attained in 71% of the patients. The remaining 27% combined the dual-release formulation with standard and/or sustained-release L-Dopa. The efficacy of treatment was assessed with the Webster Score and qualified with a mean decrease of 27% (p < 0.001) between baseline and week 14. A significant decrease of the reported adverse events such as dyskinesias and end-of-dose or wearing-off akinesias was also observed before (27 patients, 44%) and after (9 patients, 17%) the substitution (p < 0.02). These results infer that the dual-release formulation is as good as or superior to any other galenic form of L-Dopa. In conclusion, the dual-release formulation of L-Dopa either introduced or substituted for the best treatment available showed good clinical efficacy and tolerability in all stages of the evolution of idiopathic Parkinson's disease treatment in this 14-week open-label study.

Aged↗
PubMed1997

Dopa-responsive childhood dystonia: a forme fruste with writer's cramp, triggered by exercise.

An 11-year-old girl was evaluated for walking difficulties and fatigue at the end of the day in the last 2 years. Handwriting was also difficult with 'cramps' after a short time of writing. Neurological examination was normal most of the time but in the evening and after exercise, an abnormal walking posture and rare dystonic movements of the foot could sometimes be seen. The mother was found to have mild parkinsonism and is asymptomatic on L-dopa. In the daughter, all symptoms and signs disappeared on L-dopa, but returned when the drug was withdrawn. The changes on- and off-treatment were documented with videofilms and computerized analysis of writing samples. The situation has been stable during a 5-year follow-up. We draw attention to this 'forme fruste' of dopa-sensitive childhood dystonia which becomes manifest with exercise and which can easily go unrecognized. We also discuss and illustrate the methods used for the analysis of writing.

Child↗
PubMed1997

Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients.

BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the "wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (P<O.01 v placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (P<0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (P<0.05), "on" time increased by 21.3% (P<0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (P<0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.

Aged↗
PubMed1997

Bihippocampal damage with emotional dysfunction: impaired auditory recognition of fear.

A right-handed man developed a sudden transient, amnestic syndrome associated with bilateral hemorrhage of the hippocampi, probably due to Urbach-Wiethe disease. In the 3rd month, despite significant hippocampal structural damage on imaging, only a milder degree of retrograde and anterograde amnesia persisted on detailed neuropsychological examination. On systematic testing of recognition of facial and vocal expression of emotion, we found an impairment of the vocal perception of fear, but not that of other emotions, such as joy, sadness and anger. Such selective impairment of fear perception was not present in the recognition of facial expression of emotion. Thus emotional perception varies according to the different aspects of emotions and the different modality of presentation (faces versus voices). This is consistent with the idea that there may be multiple emotion systems. The study of emotional perception in this unique case of bilateral involvement of hippocampus suggests that this structure may play a critical role in the recognition of fear in vocal expression, possibly dissociated from that of other emotions and from that of fear in facial expression. In regard of recent data suggesting that the amygdala is playing a role in the recognition of fear in the auditory as well as in the visual modality this could suggest that the hippocampus may be part of the auditory pathway of fear recognition.

Affective Symptoms↗
PubMed1997

Spinal pseudoathetosis: a rare, forgotten syndrome, with a review of old and recent descriptions.

We report a patient with a cervical spinal astrocytoma who presented with athetotic hand movements. We postulate that acute pain, related to a syrinx around the operative site, contributed to the athetosis. These movements occur only after protracted, severe loss of proprioception, often in conjunction with an acute, generally painful crisis. Athetotic movements can disappear without change in proprioceptive or motor deficits when pain lessens.

Adult↗
PubMed1997

[Olivo-ponto-cerebellous degeneration. A study of 21 patients defined by the Quinn criteria].

21 patients with diagnosis of idiopathic OPCA were examined clinically and evaluated by MRI or CT-scan. On the basis of Quinn's criteria for MSA, patients were subdivided into those with probable MSA (48 p. cent) and those with possible MSA (52 p. cent). Median age at onset was 51.8 years. The initial clinical feature of the disease was ataxia, but the presence of multiple system involvement was clear in all cases. The combination of involvement of four different system (cerebellar, parkinsonian, pyramidal, autonomic) was the most common (28.5 p. cent), followed by the association of cerebellar and pyramidal features (24 p. cent). Autonomic symptoms were present in 48 p. cent of patients. CY-scan or MRI showed cerebellar and brainstem atrophy in 43 p. cent of cases. There was no relation with the duration of the disease or the severity of clinical features. Moreover brainstem auditory evoked response and EMG were not helpful in diagnosis.

Cerebellar Ataxia↗
PubMed1996

Hashimoto's myoclonic encephalopathy: an underdiagnosed treatable condition?

We report two patients with subacute diffuse encephalopathy characterized by confusion, myoclonic encephalopathy, and mild akineto-rigid extrapyramidal signs in one case and by apathy, memory deficit, and partial complex seizures in the other. Hashimoto's thyroiditis with high titers of anti-thyroglobulin antibodies was diagnosed in both patients, who were unresponsive to anticonvulsant medication, but showed rapid neurological improvement following steroid treatment. On neuropsychological examination, predominant frontotemporal dysfunction was noted. Electroencephalographic activity was remarkable for its rhythmical delta activity, unresponsive to, or even paradoxically increased by, anticonvulsant treatment. On magnetic resonance imaging, atrophy with temporal predominance was found. These observations support the idea that this potentially treatable dementia and movement disorder should be classified as a separate clinical entity.

Adult↗
PubMed1996

"Echoing approval": a new speech disorder.

We report the cases of two patients presenting a peculiar speech disorder, which we have named "echoing approval", in which the patients echo, in replying to questions in a dialogue with short phrases, the positive or negative syntactical construction of a question, or its positive or negative intonation, but without any repetition of whole or part of sentences. When asked about their symptoms, the patients replied 80% of the time with "yes, yes", "that's right", or "exactly" to positive questions and "no, no" or "absolutely not" to negative questions, regardless of their actual symptoms and oblivious to self-contradiction. In addition, when the examining doctor was speaking to a medical colleague in the patient's presence and using medical terminology that the patient did not understand, he/she agreed or disagreed with any sentence and technical word uttered in a way entirely dependent on the syntax or intonation used. To distinguish this speech disorder from echolalia or verbal perseverations, with which it may be superficially confused, we suggest that it be called "echoing approval", as it may be part one of the manifestations of the environment-dependency syndrome. This clinical picture was found to be associated with features of transcortical motor aphasia and frontal lobe signs. One patient had a bilateral callosofrontal malignant glioma and the other a probable multiple system atrophy with global deterioration, pre-eminent frontal release signs, diffuse leukoencephalopathy and multiple lacunes. On the basis of these clinical deficits and neuroimaging features, we are unable to delineate the common, or minimal, lesioned network required for this symptomatology to occur, especially in the absence of a series of patients, and with such a difference in both the location and causes of the lesions. However, bilateral frontosubcortical dysfunction was pre-eminent in the clinical picture in both patients, even though more diffuse brain pathology was seen in one, and it might be speculated that dysfunction of the bilateral orbitofrontal and frontomesial motor frontosubcortical circuits might be involved in the aetiology of this peculiar speech disorder.

Aged↗
PubMed1995

[Initiation of treatment in Parkinson disease].

Initiating treatment in a patient with Parkinson's disease requires consideration of age, degree of disease activity, and consequences of long-term treatment. In young patients, albeit dopaminergic agonists or selegiline are possible alternatives, they will never be as effective as L-dopa, and they can be used only initially in very mild cases and for a short period of time. Long-acting L-dopa is probably better after titration with standard preparations. Potential neuroprotection by selegiline has not been confirmed so far, but it acts as a mild anti-Parkinsonian. In patients over 60, it is recommended not to use anticholinergic or dopaminergic agonists, but to start with a low dose of L-dopa and increase it by a maximum of 125 mg every 7 to 10 days. Clozapine can be very useful against psychosis.

Adult↗
PubMed1995

[Toward a treatment for dementia].

The clinical manifestations of so-called 'untreatable dementias' result from neuronal dysfunction causing premature neuronal death. As long as the neurosciences won't have an explanation for the increased vulnerability and cause of death of neurons in neurodegenerative disorders, no preventive or curative treatment can be expected. So far, the treatment of dementia focuses essentially on the consequences of neuronal dysfunction or cell loss by either a palliative approach addressing psychosis, behavior or anxiety and depression, or by substitution of deficient neurotransmitters with quasi no success. Only tacrine, a cholinesterase inhibitor, now available in Switzerland, has a marginal effect in early cases, but every other substitutive approach has failed so far. Muscarinic agonists as well as antiamyloid substances will be tested soon in clinical trials. Growth factors (especially NGF) raise big hopes for the near future, but they are still under preclinical evaluation.

Aged↗
PubMed1995

Environment-driven responses in progressive supranuclear palsy.

The neurological signs and behaviors that accompany degenerative diseases associated with fronto-striatal dysfunction are incompletely described. We observed several novel environmentally-driven behaviors in seven patients with progressive supranuclear palsy (PSP). All patients had cognitive deficits with greatest impairments on tests of frontal lobe function, and frontal lobe cerebral perfusion was significantly reduced in 4 of the 5 who had single photon emission computed tomography (SPECT) brain scans. Visual grasping, in which a patient's gaze was attracted to an incidental object in the environment such as a TV set or mirror, was preeminent. Once fixed, there was inability to release the gaze and shift to another object. In other instances, removing a table placed in front of a patient or unbuckling of his seat belt would make him stand up, which was impossible on command. Similarly, playing music would induce rhythmic foot beating, which was never obtained on command. There were compulsive utilization behaviors, such as repetitively picking up and replacing the telephone for no apparent reason. As expected, there were signs of heightened facial reflexes, grasp reflexes, apraxia of eyelid opening, echolalia and echopraxia. We postulate that these stimuli-oriented behaviors stem from parietal lobe disinhibition due to fronto-striatal dysfunction.

Aged↗
PubMed1995

"Hyperneglect", a sequential hemispheric stroke syndrome.

We studied 8 patients with stroke and hemineglect, who presented with a transient active orientation and explorative behavior, turning head, eyes, and trunk in the opposite direction to any stimuli given in the neglected hemispace, as if repelled. This peculiar active behavior increased on repetitive stimulation, with the patient turning over by more than 180 degrees, with extreme rotation and opisthotonos-like extension of the axial muscles, as if looking for something behind him, his pillow or his bed. This behavior fluctuated during the day and vanished after a few days. We coined the term "hyperneglect" for this behavior, postulating a higher degree in the neglecting behavior or an additional field of hemineglect in the non neglected hemispace, or the release of repellent active behavior from parietal origin by the acute lesion. On CT, five patients showed two sequential uni- or bilateral hemispheric strokes of different ages on CT, while two patients had a large, unilateral infarct associated with hypertensive leukoencephalopathy and contralateral brain edema respectively. This behavioral syndrome seems to be associated with an acute stroke involving the frontal or parietal lobes and a previous lesion in the same or the opposite hemisphere.

Aged↗
PubMed1995

Vascular ataxic hemiparesis: a re-evaluation.

Ataxic hemiparesis is commonly considered as one of the "typical" lacunar syndromes. Using the prospective stroke registries from Lausanne and Besançon, 100 patients were selected consecutively (73% men, 27% women; age 64.7 (SD 13.6) years) with a first stroke and ataxic hemiparesis (hemiparesis or pyramidal signs and ipsilateral incoordination without sensory loss). Brain CT or MRI was performed on all patients. A primary haemorrhage was present in 5%, an infarct in 72%, isolated leukoaraiosis in 9%, and no apparent abnormality in 14%. The locations of lesions were the internal capsule (39%), pons (19%), thalamus (13%), corona radiata (13%), lentiform nucleus (8%), cerebellum (superior cerebellar artery territory) (4%), and frontal cortex (anterior cerebral artery territory) (4%). The clinical features of ataxic hemiparesis with different locations were almost identical. Only minor associated signs allowed the localisation of the lesions (paraesthesiae with a lesion in the thalamus; nystagmus or dysarthria with a cerebellar or pontine location). Crural paresis with homolateral ataxia was seen only with cortical paramedian frontal lesions. Presumed hypertensive small artery disease was not always found, but was still the leading cause of stroke, being present in 59% of the patients and in 62% of those with small deep infarcts. A potential source of embolism (arterial or cardiac) was found in one fourth of the patients. Therefore no definite association can be made between ataxic hemiparesis and lacunar infarction. In particular, so called uncommon lesion locations may not be rare. After extensive investigations a diagnosis of lacunar infarct can be retained in only slightly more than half of the cases.

Adult↗
PubMed1995

Acute hemiconcern: a right anterior parietotemporal syndrome.

Three patients developed a striking visual and motor behaviour in the acute phase of a stroke involving the territory of the right anterior parietal artery (postcentral gyrus, parts or upper and middle temporal gyri, anterior part of inferior parietal gyrus, and supramarginal gyrus). The patients concentrated on the left side of their bodies, looking at it for long periods and relentlessly rubbing, touching, pinching, pressing, lifting, and manipulating parts of the left arm, trunk, and leg with their right hand or foot. They all had severe loss of elementary sensation on the left (touch, pain, temperature, vibration, position). The behaviour was not associated with overinterest in the left hemispace apart from their own bodies. It lasted no more than a few days, disappearing when left sided sensation improved. The findings suggest an association between sensory dysfunction and this "acute hemiconcern". None of 13 patients with a mirror infarct in the left hemisphere and none of 38 patients with acute hemisensory loss due to thalamic capsular or brainstem stroke showed hemiconcern behaviour. This behaviour may result from a feeling of strangeness critically associated with hemisensory loss without hemispatial neglect, due to involvement of the right anterior parietotemporal region.

Aged↗
PubMed1995

Parietal kinetic ataxia without proprioceptive deficit.

A patient with acute onset "classic" cerebellar ataxia of the right arm without clinically detectable deep sensory loss is reported, in relation to an acute posterior parietal infarct. Wild back and forth swaying of the arm, giving away, or worsening by suppression of vision were not seen. The lesion involved area 5, parts of area 7, the angular gyrus, the middle and posterior parieto-occipital gyri, and posterior parts of the superior and middle temporal gyri. The paracentral lobule, commonly thought to be responsible for parietal ataxia, was spared. Thus posterior parietal lesions can mimick cerebellar ataxia, possibly by severing specific projections to the ventrolateral thalamic nuclei. On the basis of previous studies in primates, the superior parietal gyrus may play a major part in the ataxia presented by this patient.

Ataxia↗