Avinoam Reches

Lithium does not interact, with haloperidol in the dopaminergic pathways of the rat brain

Prophylactic treatment with lithium has been reported to prevent haloperidol-induced dopamine (DA) receptor supersensitivity. If such an effect exists, then lithium may be useful in the prevention of tardive dyskinesia, which is related to the neuroleptic-induced DA hyperfunction. In the experiments reported here chronic lithium administration had no effect on DA synthesis or utilization in the nigrostriatal, mesolimbic, or mesocortical DA pathways in the rat brain. Similarly, lithium had no effect on the increase in DA metabolism induced by the acute administration of haloperidol. Also, chronic lithium treatment failed to modify the biochemical tolerance which developed after prolonged administration of the neuroleptic drug. Supersensitivity of the presynaptic DA receptors, which was induced by prolonged exposure to haloperidol, likewise was unaffected by prophylactic lithium treatment. We conclude that lithium does not affect changes in DA metabolism or receptor supersensitivity induced by haloperidol. These results do not support the use of lithium in neurological disorders that may be related to neuroleptic-induced DA receptor supersensitivity.

Reversible central nervous system dysfunction in folate deficiency

An epileptic patient on chronic anticonvulsant drug therapy is described, in whom anaemia and neurological abnormalities including progressive dementia, bilateral pyramidal tract signs, incontinence and ataxia developed. Vitamin B12 serum levels and absorption were normal, but serum folic acid levels were low. Both the neurological disturbances and anaemia resolved following oral folic acid administration. This sequence of events in our patient suggests a cause and effect relationship between the folate deficiency and the coexistent, transient neurological syndrome.

dl-threo-DOPS as a precursor of noradrenaline

Summarydl-threo-Dihydroxyphenylserine (dl-threo-DOPS) is a non-physiological precursor of noradrenaline (NA). The formation of NA fromdl-threo-DOPS has been reported to occur in various mammalian tissue. Since NA deficiency is thought to be underlying mechanism in several neurological disorders, we studied the role of thedl-threo-DOPS as a precursor of NA. In rats treated withdl-threo-DOPS heart NA levels increased in a dose-dependent manner with maximal effect obtained 1 h after intraperitoneal injection of the drug. However, no effect ofdl-threo-DOPS on brain NA levels or DA metabolism was detected. The effect ofdl-threo-DOPS on heart NA levels was completely inhibited in the presence of carbidopa and significantly enhanced in the presence of pargyline. Under these conditions,dl-threo-DOPS had no effect on brain catecholamines. Depletion of catecholamines was obtained by pretreatment with either alpha-methyl-p-tyrosine (AMPT), reserpine or FLA-63.dl-threo-DOPS increased NA levels in the heart but not in the brain. Finally, coadministration ofdl-threo-DOPS with levodopa potentiated the effect of levodopa on brain DA metabolism. This effect was independent of peripheral dopa decarboxylase activity and was also shown in circling behaviour in rats with unilateral destruction of the nigrostriatal pathway. In rats,dl-threo-DOPS is an effective peripheral precursor of NA but the drug itself has no effect on brain catecholamines.dl-threo-DOPS may, however, enhance levodopa effects in the brain.

Morphine inhibits cyclic AMP-dependent protein kinase and ornithine decarboxylase activities in neuroblastoma X glioma hybrid cells.

Abstract The effect of morphine on neuroblastoma x glioma hybrid cells is not limited to the inhibition of adenylate cyclase activity. It is demonstrated that in morphine-treated cells there is a marked reduction in the activity of both cyclic AMP-dependent protein kinase and ornithine decarboxylase (ODC) in response to stimulation by PGE 1 . The effect of morphine is to block a cascade of events which may be crucial for the normal biochemical processes in these cells.

Valproate encephalopathy and hypocarnitinaemia in diabetic patients

Two patients with epilepsy and diabetes mellitus developed encephalopathy while on valproate monotherapy. Low plasma carnitine levels were found. Discontinuation of valproate was followed by clinical recovery and normalization of carnitine levels. Both valproate treatment and diabetes mellitus may contribute to secondary carnitine deficiency, with resultant encephalopathy. Thus, diabetic patients may be at increased risk of developing valproate encephalopathy associated with hypocarnitinaemia.

Aseptic cavernous sinus thrombosis after internal carotid arterial occlusion in polycythaemia vera.

Two patients with untreated polycythaemia vera developed intracranial internal carotid arterial occlusion followed by monocular blindness and the characteristic features of ipsilateral cavernous sinus thrombosis. Primary septic source and signs of systemic infection were absent. It is suggested that the predisposing factors in this unusual syndrome were hyperviscosity and venous sludging induced by the basic haematological disorder and progression of the thrombotic process within the internal carotid artery towards its intracavernous portion with occlusion of the ophthalmic artery and of the arterial branches which supply the walls of the sinus.

Intrafamilial heterogeneity of movement disorders : Report of three cases in one family

Abstract We report three members of a single family with an apparently autosomal dominant, nonparoxysmal, hyperkinetic movement disorder with onset in adolescence. The proband, a 56-year-old woman, manifested dystonia, tremor and myoclonus; one of her daughters exhibited myoclonus with tremor, and the other demonstrated myoclonus with chorea later accompanied by tremor and dystonia. The slowly progressive but not debilitating symptoms were restricted to the head, arms and hands and were only moderately affected by alcohol. Laboratory investigations failed to identify any abnormality, and linkage analysis excluded the region containing the DYT1 locus, indicating that the gene responsible for idiopathic torsion dystonia was not implicated in this family. While this disorder shares manifestations with myoclonic dystonia, essential myoclonus and benign chorea, the marked intrafamilial heterogeneity and the sex-limited phenotype expressed only in females of two generations appear to be unique.

Frequent misdiagnosis of adult polyglucosan body disease

Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to potentially harmful therapeutic interventions. To examine the frequency of misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30 patients diagnosed between 1991 and 2013. Diagnosis was based on the combination of typical clinical and imaging findings, reduced glycogen branching enzyme activity, and the presence of p.Y326S GBE1 mutation. Initial symptoms started in the 5th–6th decade with bladder dysfunction (47xa0%), gait problems (33xa0%) or both. Diagnosis of APBD was delayed by 6.8 (±4.8) years. Consistent signs at diagnosis were spasticity in the legs (93xa0%), decreased or absent ankle reflexes (100xa0%), bilateral extensor plantar response (100xa0%) and distal sensory deficit (80xa0%). Nerve conduction study showed invariable sensorimotor polyneuropathy, and MRI demonstrated cervical spinal cord atrophy (100xa0%) and leukoencephalopathy (97xa0%). All 30 patients were initially misdiagnosed. Common misdiagnoses included cerebral small vessel disease (27xa0%), multiple sclerosis (17xa0%), amyotrophic lateral sclerosis (17xa0%) and peripheral neuropathies (20xa0%). Consequently, 27xa0% received inappropriate therapy. In addition, lower urinary tract symptoms in 60xa0% of men were attributed solely to prostatic disorders but did not respond to medical treatment or prostatectomy. These findings suggest that despite limited clinical variability, APBD is invariably misdiagnosed and patients are often mistreated. Physicians’ unfamiliarity with the typical clinical and imaging features of APBD appears as the main reason for misdiagnosis.

Internal carotid arterial occlusion simulating extracerebral hematoma: relation to diagnosis of stroke.

ABSTRACT: In 2 elderly male patients, a progressive neurologic deficit and alteration of consciousness developed following substantial head trauma succeeded by an asymptomatic “lucid” interval. The sequence of events and the associated electroencephalographic, echoencephalographic and cerebrospinal fluid findings strongly suggested the presence of an extracerebral hematoma. The cerebral angiographic study, however, disclosed complete occlusion of the extracranial portion of the internal carotid artery in both patients. This report stresses the diagnostic difficulties sometimes encountered in relation to stroke patients.