Yi Jen Wu

The Facilitative Effect of Transcranial Direct Current Stimulation on Visuospatial Working Memory in Patients with Diabetic Polyneuropathy: A Pre–post Sham-Controlled Study

Diabetes mellitus can lead to diabetic polyneuropathy (DPN) and cognitive deficits that manifest as peripheral and central neuropathy, respectively. In this study we investigated the relationship between visuospatial working memory (VSWM) capacity and DPN severity, and attempted to improve VSWM in DPN patients via the use of transcranial direct current stimulation (tDCS). Sixteen DPN patients and 16 age- and education-matched healthy control subjects received Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Montreal Cognitive Assessment (MOCA) for baseline cognitive assessment. A forward- and backward-recall computerized Corsi block tapping task (CBT), both with and without a concurrent motor interference task was used to measure VSWM capacity. Each DPN patient underwent a pre-treatment CBT, followed by tDCS or sham treatment, then a post-treatment CBT on two separate days. We found that although patients with severe DPN (Dyck’s grade 2a or 2b) showed comparable general intelligence scores on WAIS-IV as their age- and education-matched healthy counterparts, they nonetheless showed mild cognitive impairment (MCI) on MOCA and working memory deficit on digit-span test of WAIS-IV. Furthermore, patients’ peripheral nerve conduction velocity (NCV) was positively correlated with their VSWM span in the most difficult CBT condition that involved backward-recall with motor interference such that patients with worse NCV also had lower VSWM span. Most importantly, anodal tDCS over the right DLPFC was able to improve low-performing patients’ VSWM span to be on par with the high-performers, thereby eliminating the correlation between NCV and VSWM. In summary, these findings suggest that (1) MCI and severe peripheral neuropathy can coexist with unequal severity in diabetic patients, (2) the positive correlation of VSWM and NCV suggests a link between peripheral and central neuropathies, and (3) anodal tDCS over the right DLPFC can improve DPN patients’ VSWM, particularly for the low-performing patients.

Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats

BACKGROUND Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. OBJECTIVE We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats. METHODS STZ-induced diabetic rats were subjected to either repeated anodal tDCS or sham stimulation over the medial prefrontal cortex (mPFC). Spatial working memory performance in delayed nonmatch-to-place T maze task (DNMT), the induction of long-term potentiation (LTP) in the mPFC, and dendritic morphology of Golgi-stained pyramidal neurons in the mPFC were assessed. RESULTS Repeated applications of prefrontal anodal tDCS improved spatial working memory performance in DNMT and restored the impaired mPFC LTP of diabetic rats. The mPFC of tDCS-treated diabetic rats exhibited higher levels of brain-derived neurotrophic factor (BDNF) protein and N-Methyl-d-aspartate receptor (NMDAR) subunit mRNA and protein compared to sham stimulation group. Furthermore, anodal tDCS significantly increased dendritic spine density on the apical dendrites of mPFC layer V pyramidal cells in diabetic rats, whereas the complexity of basal and apical dendritic trees was unaltered. CONCLUSIONS Our findings suggest that repeated anodal tDCS may improve spatial working memory performance in streptozotocin-induced diabetic rats through augmentation of synaptic plasticity that requires BDNF secretion and transcription/translation of NMDARs in the mPFC, and support the therapeutic potential of tDCS for cognitive decline in diabetes mellitus patients.

Somatosensory rub evoked reflex epilepsy of a temporal lobe origin

Somatosensory rub reflex epilepsy, evoked by prolonged or repetitive cutaneous contact of a circumscribed body area, is an unusual form of reflex epilepsy. The peculiar complaints and the negative interictal electroencephalographic (EEG) recordings make it difficult to identify the epileptic origin. Here we report an unusual case whose seizures would be evoked by a touch or rub on a unilateral arm and shoulder, with a contralateral temporal lobe origin, demonstrated in immediate postictal single-photon emission computed tomography (SPECT).

Lamotrigine-induced hypersensitivity syndrome in a Han Chinese patient with the HLA-B*5801 genotype

Antiepileptic drug (AED) therapy is the mainstay for treating epilepsy. Most of the adverse effects in AED therapy are mild, predictable, and dose-dependent. Cutaneous eruptions, which lead to drug withdrawal and hospitalization, are the most frequent idiosyncratic adverse reactions. Severe cutaneous adverse reactions (SCARs) with high morbidity and mortality, including Stevens– Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome, are not uncommon in AED therapy. A strong association between the allele of human leukocyte antigen HLA-B*1502 and carbamazepine-induced SJS has been found in Han Chinese [1]. The lower incidence of carbamazepine-induced SJS in Caucasians, in contrast to its higher incidence in Han Chinese, suggests that there is an ethnic difference in susceptibility. Lamotrigine, one of the newer AEDs, has been reported as a risk factor for skin rashes. We previously [2] identified the risk factors of skin rashes in the patients treated with an initially high dose and rapid escalation of the dose of lamotrigine, and co-medicated with valproic acid. The role of HLA B*1502 in lamotrigine-induced SJS has been investigated and no definite association was found in the studied Han Chinese population [3], which is the same as in Caucasians. In contrast, there seems to be a weak association between HLA B*5801 and lamotrigineinduced SCARs in Caucasians [4]. We report a female Han Chinese patient with epilepsy and lamotrigine-induced SCARs; a genetic study identified the HLA-B*5801 allele as a risk factor. A 32-year-old Han Chinese woman with epilepsy, treated in a special epilepsy clinic in National Cheng Kung University Hospital for years, had been given regular valproic acid therapy (400 mg/day) and had a seizure frequency of around once a month. As the frequency had increased to around once a week, lamotrigine (starting at 20 mg/day, with a 20 mg/week increase) was added. Four weeks later, with the lamotrigine dose at 100 mg/day, she was admitted because of a high fever, generalized erythema, and jaundice. The patient’s blood test revealed high levels of AST (413 U/L), GPT (496 U/L), total bilirubin (17.7 mg/dL), LDH (790 IU/L), alkaline phosphate (582 IU/L), and gamma-GT (821 U/L). Combined with the high fever and a generalized rash, the patient was diagnosed with drug hypersensitivity syndrome. A skin biopsy (Fig. 1) showed mild spongiosis and scattered necrotic keratinocytes in the spinous layer, and vacuolar interface alteration of the basal layers with an infiltration of small lymphocytes. She also showed a perivascular infiltrate of small lymphocytes with scattered neutrophils in the upper dermis. These findings are consistent with maculopapular drug eruption. Under the diagnosis of lamotrigine-induced SCARs, we performed genotyping for this patient and the results showed the J. C. Chow Y.-J. Wu J.-J. Tsai Department of Pediatrics, Chi-Mei Foundation Medical Center, Tainan, Taiwan

Two gloves and one sock syndrome after a pontine hemorrhage

Introduction:Stroke presenting with paresthesia of bilateral hands and one leg in a gloves-and-one-sock distribution is rare. Case report:We report a patient with brainstem hemorrhage involving the right medial lemniscus (ML) across the midline to the medial part of left ML that resulted in paresthesia in bilateral hands and the left foot. The neighboring lesions include the right ventral trigeminothalamic tract causing left facial numbness, right trigeminal motor nucleus leading to right lateral pterygoid muscle weakness, right anterolateral tract resulting in a left hemisensory syndrome, and the right superior cerebellar peduncle decussation causing left limb ataxia. Conclusions:The paresthesia of bilateral hands and one lower leg in a pattern of 2-gloves-and-1-sock has localizing value and indicates a brainstem lesion involving the bilateral MLs.

Contraversive shift of conjugate eye deviation in hemispheric stroke indicates emerging mass effect

Conjugate eye deviation (CED) towards the ipsilateral or the contralateral side of the brain lesion can occur as a result of acute hemispheric stroke. To our knowledge, there have been no reports of CED shifting from the lesional side to the contralateral side in acute hemispheric stroke in the literature. We present four patients with right hemispheric stroke with a forced CED shift from the right to the left side during the acute stage with corresponding mass effect on the right internal capsule and right thalamus, as shown on brain imaging. Mass effect on thalamic mediated circuits and the corticopontine projection within the internal capsule probably underlies this CED shift via the dynamic balance of oculomotor control between the two hemispheres. Contraversive CED shift is a potentially useful early predictor of emerging mass effect in acute hemispheric stroke.

Nonketotic hyperglycemia-related reflex epileptic seizures induced by Mah-Jong playing

Seizures related to nonketotic hyperglycemia (NKH) are often encountered in clinical practice. Among such seizures, reflex seizures are rare, and most of them are movement-induced focal seizures. We describe five patients with NKH and reflex seizures induced exclusively by playing Mah-Jong, a traditional and popular game in Chinese society. Four patients had partial seizures and one had a generalized seizure. All the patients manifested NKH on occurrence of the seizure. During Mah-Jong in the presence of NKH, seizures could arise from the frontal and temporal lobes, which are highly activated during the game. Both avoidance of Mah-Jong playing and control of glucose intake help prevent this disorder.

Teaching Video NeuroImages: Cold-induced eyelid myotonia

A 48-year-old man presented with episodic paraplegia and stiffness of hands, face, and tongue, along with eyelid myotonia when exposed to cold temperature, which he had since childhood. Eyelid myotonia was evoked either by exposure to cold weather (video on the Neurology® Web site at www.neurology.org and figure 1) or by forceful eye closure. Myotonia was elicited with percussion of the tongue and thenar eminence. EMG showed myotonic discharge at room temperature (figure 2). Creatine kinase was mildly elevated to 293 U/L. The genetic study showed missense mutation (R1448C) in the voltage-gated sodium channel, type IV, alpha subunit (SCN4A).1 The patients daughter had the same genetic mutation and similar symptoms.

Reversible postvaccination paraneoplastic encephalomyelitis in a patient with lung adenocarcinoma

ABSTRACT Encephalomyelitis occurs in paraneoplastic syndrome and acute disseminated encephalomyelitis through different autoimmune mechanisms. No postvaccinal encephalomyelitis other than acute disseminated encephalomyelitis has been reported in patients with malignancy. A 68-year-old woman was admitted because of a headache followed by a gait disturbance and psychomotor retardation 2 days after she had received an influenza vaccination followed by abulia, limb rigidity and hyperreflexia of both legs, and meningeal irritation. Cerebrospinal fluid studies showed increased intracranial pressure, elevated immunoglobulins G and A, and pleocytosis. Contrasted brain magnetic resonance imaging revealed ventriculomegaly and multiple symmetric leptomeningeal enhancement, without demyelinating changes or cortical ribbon signs. Somatosensory evoked potentials and nerve conduction velocity studies suggested myelitis. Encephalomyelitis was diagnosed on the basis of clinical and laboratory examinations. The etiological survey identified a lung adenocarcinoma. Both the encephalomyelitis and the lung adenocarcinoma simultaneously progressed after the vaccination and then, after targeted therapy for lung cancer, simultaneously subsided. In conclusion, postinfluenza-vaccination paraneoplastic encephalomyelitis may occur in patients with lung adenocarcinoma.