Catecholamine utilization in specific rat brain nuclei after short-term hyperprolactinaemia

Endogenous hyperprolactinaemia was induced in intact male rats by transplantation of pituitaries under the kidney capsule. Five days later the utilization of noradrenaline (NA) and dopamine (DA) in individual brain nuclei and changes of plasma prolaction (PRL) were measured. Inhibition of catecholamine synthesis by alpha-methyl-p-tyrosine (alpha-MPT) was used to measure utilization. Hyperprolactinaemia increased the utilization of NA in the locus coeruleus, the cell-body region of the dorsal noradrenergic bundle (DNB), but decreased it in some terminal projections of the same pathway (e.g. the cingulate gyrus). DA utilization was increased by hyperprolactinaemia in the eminentia mediana. In the nigrostriatal DA-ergic projection, hyperprolactinaemia decreased the utilization of DA in the cell-body region (substantia nigra) and increased it in the terminal projection (nucleus caudatus). In the ventral tegmental area (mesolimbic DA-ergic projection), hyperprolactinaemia decreased the utilization of DA. It is concluded that hyperprolactinaemia affects neurotransmission in the hypothalamus and also in specific extrahypothalamic pathways (e.g. DNB, nigrostriatal and mesolimbic DA-ergic projections) and that these changes may correlate with some behavioural effects of the pituitary hormone.     

Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.     

Drug‐induced and psychogenic resting suprahyoid neck and tongue tremors

We describe three patients who presented with 4 to 5 Hz tremors of the suprahyoid region of the neck. Two developed their tremors in association with levosulpiride treatment. When they opened their mouths, the neck tremors disappeared; no tongue tremors were observed. However, a videofluoroscopic examination showed the presence of tongue tremors at rest. The remaining patient had a psychogenic tremor. © 2008 Movement Disorder Society     

Unilateral rubral tremors in Wilson's disease treated with dimercaprol

Tremors are reported as the most frequent neurological manifestation of Wilson''s disease (WD) in some series. Postural tremors, rest tremors, action tremors and wing-beating (rubral) tremors are the different types of tremors seen in WD. We report a patient of WD with unilateral rubral tremors refractory to 1-year therapy with Penicillamine and anti-tremor medications. The tremors decreased considerably after adding chelation therapy with dimercaprol. Combination of Penicillamine and dimercaprol is an effective decoppering measure in rubral tremors of WD.     

The relationship between valproate induced tremors and circulating neurotransmitters: a preliminary study

Patients with epilepsy and on valproate (VPA) therapy may develop tremors as a common adverse effect; however, its exact mechanisms are unknown. We hypothesize that VPA-induced tremors may be related to the disturbances in dopamine (DA) and catecholamines (norepinephrine (NE) and epinephrine (E)) concentrations (which are also involved in VPA anticonvulsant effect). We aimed to determine the frequency and type of VPA-induced tremors and their risk factors and to investigate whether or not they are related to the plasma DA, NE and E concentrations. This study included 75 adults with primary epilepsy (mean age: 31.90 ± 5.62 years) and on VPA therapy for 10.57 ± 3.55 years and 40 matched healthy controls. Patients were divided according to the absence or presence of tremors. Blood samples were analyzed for DA, NE and E. Intermittent action tremors in both hands were reported in 31 (41.33%). Chronic standard VPA therapy, older age, longer treatment duration and higher serum concentrations of VPA are risk factors for tremors. None of the patients on controlled release VPA had tremors. Compared to controls, patients (without and with tremors) had lower DA (p = 0.0001) and NE (p = 0.01) concentrations. Compared to patients without tremors, patients with tremors had lower levels DA (p = 0.045) and NE (p = 0.01). Significant correlations were identified between DA with NE (r = 0.540, p = 0.001) concentrations and serum VPA with DA (r = ?0.285, p = 0.045) and NE (r = ?0.358, p = 0.01) plasma levels. We conclude that benign action tremors are common with standard VPA. Mechanisms underlying VPA-induced tremors may involve abnormalities of DA and NE neurotransmitters.     

Clinical and neurophysiologic spectrum of orthostatic tremor: case series of 26 subjects.

Orthostatic tremor (OT) is a condition described as high-frequency tremors predominantly in the legs and trunk, which are present not only in the standing position but also during isometric contraction of the limb muscles. This report is one of the largest OT series describing clinical and neurophysiologic findings in 26 subjects with OT. The main findings included 13.0 to 18.6 Hz leg tremors while standing with varied patterns of phase relationships between the antagonists of the ipsilateral leg and between the homologous muscles of the contralateral leg, short latency tremor onset upon standing with abrupt cessation after sitting, coexistence of tremors in the cranial structures and the arms, and sense of unsteadiness without actual falls. Although the oscillator of OT is most likely located in the brainstem, cerebral cortex, basal ganglia, and cerebellum may also be involved in its pathogenesis.     

On the neurotoxicity of chlordecone: a role for gamma-aminobutyric acid and serotonin

Rats receiving the chlorinated insecticide, chlordecone (80 mg/kg i.p.), exhibit hyperexcitability, exaggerated startle response and tremors within a few hours after the injection. Since the chlordecone-elicited tremors are relieved by injections of muscarinic receptor blockers, acetylcholine has been implicated indirectly in the mechanism of chlordecone toxicity. Our studies on acetylcholine steady-state levels and turnover in several brain structures failed to detect evidence for an involvement of cholinergic presynaptic mechanisms in the chlordecone toxicity. We then investigated whether GABA is involved by measuring the rate of its accumulation following intraventricular injection of gabaculine. Chlordecone reduced the rate of GABA accumulation in striatum, but not in cerebellum, brainstem or hippocampus. Such inhibition appeared 4 h after drug injection thereby preceding the onset of tremors. Since tremors elicited by chlordecone are attenuated by the administration of serotonin receptor blockers and since chlordecone increases serotonin (5-HT) turnover, we studied whether 5-HT recognition sites are modified following chlordecone administration. We have found a reduction of the Bmax of 5-HT1 receptors in striatum and hippocampus without any modification in the kinetic characteristics of 5-HT2 receptors. We have also shown that the temporal relationship between down regulation of 5-HT1 recognition sites, reduction of striatal GABA turnover and tremors caused by chlordecone allows one to consider these 3 phenomena as reciprocally dependent. In conclusion our results favor the possibility that tremors may result from a decrease in the striatal GABergic tone which probably is elicited by an increase of serotonergic activity caused by chlordecone by a yet unknown mechanism.     

A single oral dose of cannabidiol did not reduce upper limb tremor in patients with essential tremor

Essential tremor (ET) is a common clinical syndrome characterized by action tremors affecting both upper limbs that can compromise manual tasks' execution and impair functional and social performance. The primary pharmacological treatment is symptomatic, but effective medicines are somewhat limited. There is a clear need to find new effective therapies for the treatment of ET. Cannabidiol (CBD) is a modulator of CB1 receptor and CB1 agonists can reduce tremors in experimental models. We hypothesized that a single acute CBD intake would reduce tremors in ET patients. We performed a randomized, controlled, double-blind, crossover study on 19 patients with ET. They were 10 males and 9 females, had mean 63 years of age, and mean 23 years of disease duration and had insufficient control of their tremors with the usual pharmacological treatment. They ingested a single oral dose of CBD (300 mg) or placebo in two experimental sessions performed 2-weeks apart. Patients were evaluated immediately before and after oral ingestion (60 min and 210 min), using the Fahn-Tolosa-Marin clinical scale. There was no carryover effect. There were no significant differences in upper limb tremors score, specific motor task tremor scores (writing and drawing/pouring) or clinical impression of change after treatment with placebo or CBD. In conclusion, a single 300 mg oral dose of CBD had no significant effect on the severity of upper limb tremors of ET patients. Our findings did not exclude the possibility that chronic treatment with CBD could have a symptomatic effect.     

Kinetic predominant essential tremor: successful treatment with clonazepam

Fourteen patients with marked kinetic tremors of long duration but no other major neurologic signs are described. A positive family history of essential tremor, mild postural tremor, and tremor suppression with alcohol suggest that the condition is a variant of essential tremor. Kinetic tremors had a frequency of 3.5 to 6.0 Hz and an alternating EMG pattern. Propranolol caused improvement in some patients, but clonazepam treatment resulted in tremor suppression in all patients. Kinetic tremor without cerebellar signs is a subtype of essential tremor with pharmacologic responsiveness to clonazepam.     

Side-to-side correlation of muscle activity in physiological and pathological human tremors.

OBJECTIVE: Many tremors occur always or often bilaterally. The question arises whether this could be explained by a common source or commonly transmitting pathways or by bilaterally represented, independent structures with the same oscillatory properties. A similar tremor frequency does not provide sufficient information to clarify this question. METHODS: We analyze coherencies between surface electromyographies (EMG) to investigate if bilateral physiologic (PT), essential (ET), Parkinsonian (PD) and orthostatic (OT) tremors originate from a common source for both sides of the body. We show that commonly used techniques to test whether coherencies are significant could lead to false positive results for tremor EMGs. A new estimation procedure is proposed to test EMG tremor time series on their linear independence. We apply this test to bilateral tremors. RESULTS: All measured EMG-pairs in OT (n = 7) were highly coherent between both sides with reproducible coherency values of up to 0.99. All other investigated tremors, i.e. PT and enhanced physiological tremors (EPT, n = 117), ET (n = 76) and PD resting and postural tremors (n = 70) do not show a significant side-to-side correlation. CONCLUSIONS: This finding shows that the pathophysiologies of OT and other pathological tremors are definitely different. Either they have different origins or different kinds of transmitting pathways. The proposed method might also be used to investigate other electrophysiological data and is a helpful, easy to use investigation for a daily clinical routine.