Takayuki Jo

Reward-Induced Phasic Dopamine Release in the Monkey Ventral Striatum and Putamen.

In-vivo voltammetry has successfully been used to detect dopamine release in rodent brains, but its application to monkeys has been limited. We have previously detected dopamine release in the caudate of behaving Japanese monkeys using diamond microelectrodes (Yoshimi 2011); however it is not known whether the release pattern is the same in various areas of the forebrain. Recent studies have suggested variations in the dopaminergic projections to forebrain areas. In the present study, we attempted simultaneous recording at two locations in the striatum, using fast-scan cyclic voltammetry (FSCV) on carbon fibers, which has been widely used in rodents. Responses to unpredicted food and liquid rewards were detected repeatedly. The response to the liquid reward after conditioned stimuli was enhanced after switching the prediction cue. These characteristics were generally similar between the ventral striatum and the putamen. Overall, the technical application of FSCV recording in multiple locations was successful in behaving primates, and further voltammetric recordings in multiple locations will expand our knowledge of dopamine reward responses.

Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome

To the Editor: Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adultonset hereditary neurodegenerative disease underpinned by expansion of the premutation in the CGG trinucleotide repeats in the fragile mental retardation gene 1 (FMR1) (1). The prevalence of the FMR1 premutation is approximately 1/250 in women and 1/800 in men. Therefore, while the prevalence of FXTAS in men is estimated to be approximately 1 in 3000 to 6000 in general population, the prevalence in women is thought to be much lower (1,2). The syndrome clinically presents with postural and action tremors, cerebellar ataxia, cognitive deficits, parkinsonism, dysautonomia, and neuropathy (3), although exact manifestations can be variable among sufferers. Although there is not enough evidence of treatment for FXTAS, tremor in FXTAS can be treated with medications such as primidone, beta blockers, benzodiazepines, and memantine (4). Hall et al. reported that 50% of patients had mild to moderate improvement on primidone, that 37.5% had moderate improvement on beta blockers, and that 25% had moderate improvement on benzodiazepines (4). In patients with medication refractory FXTAS-associated tremor, ventral intermediate (Vim) nucleus of the thalamus deep brain stimulation (DBS) has been applied (5–10). Out of eight cases of Vim DBS, two have resulted in the worsening of balance and ataxia symptoms (5,10). Recently, posterior subthalamic area (PSA) stimulation has been suggested as an alternative option for control of severe tremor beyond essential tremor (ET) (11). Although there is no consensus to date regarding the best DBS target for patients with FXTAS, there has been a concern that the traditional Vim target would provide insufficient benefit, especially in cases of proximal tremor. We conducted a retrospective chart review of a single case of PSA DBS for a patient with the FXTAS mutation. This study was approved by the Institutional Review Board of Juntendo University School of Medicine.

A patient with demyelination, laminar cortical necrosis, and rhabdomyolysis associated with hypernatremia.

A 60-year-old man with renal failure and intraabdominal abscess formation probably due to perforation of the colon underwent laparotomy on the sixth hospital day. He developed respiratory infection, deterioration of renal failure, and heart failure resulting in severe respiratory insufficiency after laparotomy. He was placed on mechanical ventilation using sedatives and muscle relaxant and was treated with antibiotics, steroids, and a diuretic. The value of serum sodium jumped from 146 to 164 mEq/L in 2 days. Sodium infusion was discontinued, and hypernatremia decreased. He fell into a coma and demonstrated generalized convulsions after mechanical ventilation was discontinued. His head computed tomography did not indicate any pathologic findings, and his convulsions were not controlled so that he was again placed on mechanical ventilation. The laboratory findings revealed rhabdomyolysis (18936 IU/L) 5 days after the normalization of hypernatremia. Mechanical ventilation and hemodialysis were terminated after the convulsions were controlled and the renal failure improved on the 82nd hospital day. Head magnetic resonance imaging exhibited that multiple hyperintensity lesions in the white matter with linear signal changes in both occipital cortex. He remained unconscious for 6 months. This is the first case that demonstrated demyelination, laminar cortical necrosis, and rhabdomyolysis associated with hypernatremia. Rhabdomyolysis after rapid occurrence of hypernatremia might be a laboratory sign of concomitant demyelination.

Interleaving stimulation with a combination of bipolar and monopolar configurations for secondary failure of bilateral subthalamic stimulation in Parkinson's disease

Current control technology using interleaving stimulation could be theoretically useful for maximizing the benefits of deep brain stimulation, but it is seldom reported. A 61‐year‐old man with young‐onset Parkinsons disease was previously treated with bilateral subthalamic nucleus deep brain stimulation because of wearing‐off and peak‐dose dyskinesia; he again developed wearing‐off and a gait disturbance 3 years after surgery. His deep brain stimulation was adjusted by utilizing interleaving stimulation with a combination of monopolar and bipolar configurations, because increasing stimulation with single or double monopolar stimulation, and interleaving monopolar stimulation caused pyramidal side‐effects. After adjusting deep brain stimulation, his wearing‐off symptoms and gait disturbance were markedly improved without any side‐effects. The present case report describes the potential of interleaving stimulation with a combination of monopolar and bipolar settings for the treatment of Parkinsons disease.

Rescue pallidal stimulation for diphasic and stimulation-induced dyskinesia after successful subthalamic stimulation for Parkinson's disease

A 64‐year‐old woman with Parkinsons disease who developed motor fluctuations, and both levodopa‐induced and stimulation‐induced dyskinesia, after long‐term treatment of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), underwent implantation of additional globus pallidus internus (GPi) DBS leads. Although an appropriate DBS target should be chosen, “rescue” GPi DBS can synergistically work with pre‐existing STN DBS for the treatment of dyskinesia, which might provide a “third honeymoon.”

“Two Odd Targets” Strategy in Deep Brain Stimulation for Parkinson's Disease With Unilateral Levodopa Induced Dystonia

A 49‐year‐old man with Parkinsons disease developed wearing‐off and levodopa‐induced dyskinesia with a dystonic component in the left upper limb. He decided to undergo deep brain stimulation. Asymmetric targets were chosen; for the right side, globus pallidus interna was selected to improve the dystonia in his left upper extremity, and for the left side, the subthalamic nucleus, which had the expected benefit of reducing the patients medications, was selected. After the surgery, the levodopa‐induced dystonia in his left arm was markedly improved, and the levodopa equivalent dose was reduced by 21.4%. The present case suggests that deep brain stimulation with a different target in the left and right hemisphere could be an effective therapeutic option for patients with asymmetric symptoms.

Effect of zonisamide on post‐traumatic Holmes’ tremor

Holmes’ tremor is a rare symptom characterized by a complex combination of resting, postural and intention tremor. A 66‐year‐old right‐handed man post‐traumatically developed severe action tremor in his right hand, which had a component of the re‐emergent type and predominantly involved proximal muscles. He also presented mild resting tremor in his right hand. As the response of levodopa/carbidopa and arotinolol was limited, he started zonisamide, which resulted in dramatic improvement. The Fahn–Tolosa–Marin Tremor Rating Scale motor score improved from 52 points to 24 points. In conclusion, zonisamide could be a therapeutic option for post‐traumatic Holmes’ tremor. Further prospective studies are required.