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Hyperkinetic Movement Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Morales-Briceno Hugo, Victor S.C. Fung, Annu Aggarwal, Philip Thompson
May be as useful as beta-blockers, but adverse effects are common. Care is required when introducing primidone because of acute nausea, sedation, and unsteadiness, which may warrant stopping the drug. A low starting dose minimizes adverse effects, particularly if taken in the evening before retiring. There may be no added benefit increasing the daily dose beyond 250 mg.
Partial Seizures
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Both phenytoin (PHT) and carbamazepine (CBZ) have been found to be effective in the treatment of partial seizures. Reynolds et al. (1) and Shorvon et al. (2) have shown that both partial and generalized seizures respond to PHT. However, the control of partial seizures was less impressive than the control for generalized attacks (2). Feely et al. (3) studied the response to PHT in patients with generalized and partial seizures. A total of 31 patients were studied; 20 were taking PHT prescribed as monotherapy. While 47% of patients with generalized seizures achieved complete freedom from attacks for a minimal period of 6 months, only 17% of patients with partial seizures achieved a similar response. Callaghan et al. (4) reported the effects of CBZ prescribed as single drug treatment for patients with generalized or partial seizures. Seventeen patients with partial seizures were studied, and only five achieved complete control. Shorvon et al. (2) have also shown that CBZ is effective in the control of partial seizures. Although phenobarbital (PB) has been available for the treatment of epilepsy for many years, there is very little information available in the literature on the effects of PB on partial seizures when prescribed as single drug treatment. Feely et al. (5) studied the effects of PB on epilepsy in previously untreated patients. Four patients had complex partial seizures (CPSs). Three patients became seizure-free and one patient improved. Earlier studies of primidone (PRM) as monotherapy (6–8) indicate that PRM is effective in the control of partial and generalized seizures.
Antiepileptic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Primidone is indicated in the United States for patients with focal or generalized epilepsy, but it has been replaced by carbamazepine and other newer AEDs that possess lower incidence of sedation in recent times. Primidone’s antiseizure effects are due to its two active metabolites: phenobarbital and phenylethylmalonamide (PEMA) (Baumel et al., 1972).
Deep brain stimulation and other surgical modalities for the management of essential tremor
Published in Expert Review of Medical Devices, 2020
Kai-Liang Wang, Qianwei Ren, Shannon Chiu, Bhavana Patel, Fan-Gang Meng, Wei Hu, Aparna Wagle Shukla
Essential tremor (ET) is one of the most common movement disorders in clinical practice characterized by a 4–12 Hz tremor and prevalence of up to 4.0% in over 65 years or older population [1–3]. ET manifests as a bilateral action tremor of the upper limbs and, in some cases, is accompanied by a tremor of the head, voice, or lower limbs. ET can profoundly impact the quality of life, especially in patients with severe disabling tremors, who usually have difficulty in finishing daily tasks such as eating, drinking, taking showers, dressing, and writing. Some ET patients with uncontrollable tremor experience a social embarrassment. Primidone and propranolol are commonly prescribed oral pharmacological medications for ET. However, at least 30–50% of patients do not respond to these medications [4]. Surgical techniques are employed by the neurosurgeons as potent alternative treatments for these ET patients. These include ablation procedures such as radiofrequency (RF) thalamotomy, gamma knife radiosurgical (GKRS) thalamotomy, focused ultrasound (FUS) thalamotomy and stimulation procedure such as deep brain stimulation (DBS) targeted to ventral intermediate nucleus (Vim) of the thalamus [5–7]. Also, DBS can be targeted to the posterior subthalamic area (PSA) [8,9] that includes prelemniscal radiation or the cerebello thalamic tract (CTT) [10,11] and caudal zona incerta (cZI) [12,13]. In this narrative review, we plan to discuss the technical aspect of the procedures, advantages, limitations, and treatment outcomes for the above surgical treatment modalities.
Brain circuits and neurochemical systems in essential tremor: insights into current and future pharmacotherapeutic approaches
Published in Expert Review of Neurotherapeutics, 2018
Sara M Schaefer, Ana Vives Rodriguez, Elan D Louis
Primidone is not the US FDA-approved for ET but, along with propranolol, it is recommended as a first-line treatment [44]. The mean reduction in tremor amplitude as measured by accelerometry across four class I studies was approximately 50%. Primidone’s mechanism of action is not well understood; its antiepileptic effects have been primarily ascribed to one of its metabolites, phenobarbital, a nonselective GABAA receptor agonist. However, one study demonstrated that primidone’s effect in ET occurs prior to detection of phenobarbital in the blood stream [46]. In addition, primidone is superior to phenobarbital in its treatment of ET – phenobarbital has level U evidence for use in ET [44]. Primidone’s other major metabolite, phenylethylmalonamide, also does not significantly impact tremor [47,48]. Similarly, at the frog neuromuscular junction, primidone dose-dependently increases neurotransmission and end-plate potential, while phenylethylmalonamide does not [49]. These findings suggest that primidone exerts its therapeutic effect independent of its by-products [44,47,50]. Despite this determination, there is a paucity of literature that seeks to explain primidone’s true mechanism of action separate from those of its metabolites. One MRI spectroscopy study found that primidone use did not impact GABA levels in the dentate nucleus [48]; this may suggest that primidone acts more selectively on GABAA receptors with specific subunits, as opposed to phenobarbital, which acts nonselectively. As noted earlier, primidone does not eradicate tremor – the mean reduction in tremor amplitude as measured by accelerometry across four class I studies was approximately 50%. This could be due to the diffuse effects of nonselective GABAA receptor agonism by its metabolite phenobarbital, creating competing/canceling effects in terms of PC output.
Therapeutic strategies for treating epilepsy during pregnancy
Published in Expert Opinion on Pharmacotherapy, 2019
The safety of breastfeeding while taking AEDs is understandably a concern for WWE in the postpartum period and counseling in relation to this issue is important, and should be done in advance. Concerns are not unfounded, given the fact that the blood-brain barrier is not well-formed until well after birth, thus leaving the infant’s brain relatively unprotected [75]. The benefits of breastfeeding are well documented, therefore evidence to support its safety in WWE has been crucial in making decisions about feeding. The 2009 AAN practice parameter [4] did not give a definitive recommendation in this regard but did discuss breast milk penetration of AEDs. Primidone and levetiracetam probably penetrate into milk in potentially clinically important amounts. Gabapentin, topiramate, and lamotrigine possibly penetrate into breast milk in clinically important amounts, whereas phenytoin, phenobarbitone, carbamazepine, and valproate probably do not penetrate into milk in clinically important amounts. The NEAD [9] study has fortunately addressed this issue. It was found that 6-year-old children who had been breastfed on AEDs had an IQ of 4 points higher (CI 0–8) with a verbal index 4 points higher (CI 0–7) versus those who were not [76], thus alleviating concerns of harmful effects of breastfeeding with AEDs. Overall breastfeeding should be encouraged in WWE, but this needs to be balanced also with the need for adequate sleep. Infants should be monitored for any potential adverse effects, when the mother is using an AED that has the potential to accumulate, and infant serum levels may be measured if side effects are suspected. A common recommendation in WWE would be to enlist the help of family members in giving one or two supplementary bottle feeds of expressed milk or formula each 24 h, to ensure that a stretch of uninterrupted sleep is possible [77]. Practical safety advice should be given for postpartum infant care including changing the newborn on a changing mat on or close to the ground and not bathing an infant unsupervised in the event of a seizure [78].