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• The cerebellar-motor loop has been implicated as a key anatomical region associated with dystonia.

Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms., This study presents mathematical models that explain the effect of temporally patterned electrical stimulation on cortical oscillations and provides supporting evidence using data recorded directly from human cortex during transcranial electrical stimulation., Author Summary Rhythms in the brain are believed to play an important role in cognition. Disruptions in these oscillations are associated with a number of neurological and psychiatric disorders. Therefore, noninvasive brain stimulation techniques that target these oscillations offer promise as therapeutic tools. In particular, transcranial alternating current stimulation (tACS) applies a periodic stimulation waveform to engage specific oscillations in the cortex. Although recent studies provide evidence for the modulation of cortical oscillations by tACS, the exact mechanism by which the effects are produced is poorly understood. We propose two mathematical models of interaction between periodic electrical stimulation and ongoing brain activity that may explain the effects of tACS. In addition, we present a unique dataset in which we stimulated the patients’ cortical surface with subdural electrodes and observed the responses to stimulation in neighboring electrodes. We found that stimulation enhanced ongoing oscillations both during and immediately after stimulation. This enhancement depended on the brain state, thereby supporting our proposed models. Our results demonstrate the effect of electrical stimulation on cortical oscillations and highlight the importance of considering the state of the brain when designing electrical stimulation therapies for disorders of the central nervous system.

White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer's disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.

To evaluate the interhemispheric interaction of paired associative stimulation (PAS)-induced plasticity, we performed a transcranial magnetic stimulation study on nine healthy volunteers after PAS, motor evoked potentials were significantly enhanced in both the nonstimulated and stimulated primary motor cortex (M1). Short-interval intracortical inhibition and intracortical facilitation were not changed in the nonstimulated M1, but interhemispheric inhibition was significantly reduced after PAS. Motor evoked potential enhancement in the nonstimulated M1 was significantly correlated to that in the stimulated M1 and tended to correlate with the degree of pre-PAS interhemispheric inhibition. These results show that PAS-induced plasticity in the dominant M1 can transfer to contralateral M1 depending on the amount of plastic change induced in the stimulated M1 and, also probably, on the amount of transcallosal connection.

Although restless legs syndrome (RLS) and akathisia have similar clinical manifestations and seem to share a common pathophysiology, they are regarded as distinct clinical syndromes. We present three patients with acute pontine infarction and RLS or akathisia as clinical manifestations. They presented with abrupt onset of restlessness of various body parts, as well as other neurological signs including dysarthria or weakness of the legs. Brain MRI of all three patients showed acute pontine infarction. The clinical syndrome in two of the patients was compatible with RLS and one with akathisia. Their symptoms improved after a brief period. Our finding of secondary RLS and akathisia as manifestations of acute pontine infarction provides information that assists in understanding the common anatomical and pathophysiological basis of RLS and akathisia.

We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer’s disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD (n = 61), with no subcortical WM ischemia, and healthy control patients (n = 33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p < 0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.

Charles Bonnet syndrome (CBS) is characterized by the occurrence of complex visual hallucinations in visually impaired patients who understand that what they see is unreal. The pathophysiologic mechanism of CBS is poorly understood. However, hypermetabolism of the thalamocortical pathway as a result of deafferentation was recently proposed as a possible mechanism. A 69-year-old patient with CBS presented with a 5-year history of visual hallucinations after bilateral visual impairment, which had progressed to troublesome images of many unreal people and animals. Positron emission tomography-statistical parametric mapping (PET-SPM) imaging studies initially revealed hypermetabolism in the right inferior temporal area and left thalamus, which disappeared after treatment with valproic acid. This case, using PET-SPM analysis, supports the thalamic hypermetabolism theory of CBS.

Levosulpiride is a substituted benzamide that is widely used for the management of dyspepsia and emesis. However, little is known about levosulpiride-induced movement disorders (LIM). The aim of this study was to investigate the clinical characteristics of patients with LIM. Among 132 consecutive patients who were diagnosed with drug-induced movement disorders between January 2002 and March 2008, 91 patients with LIM were identified and their medical records reviewed. Seventy-eight (85.7%) patients were aged more than 60 years. The most common LIM was parkinsonism (LIP) (n = 85, 93.4%), followed by tardive dyskinesia (n = 9, 9.9%) and isolated tremor (n = 3, 3.3%). Twenty-one (24.7%) of the 85 patients with LIP were rated as Hoehn and Yahr stage III-V. The oro-lingual area was the only body part that was involved by tardive dyskinesia. LIM persisted after withdrawal of levosulpiride in 48.1% of patients with LIP, 66.7% with dyskinesia, and none with isolated tremor. None of clinical and MRI features predicted the reversibility of LIP. Levosulpiride frequently causes drug-induced movement disorders, presenting mainly with LIP followed by lower face dyskinesia. The symptoms are often severe, and irreversible even after the withdrawal of levosulpiride. Physicians should be cautious in using levosulpiride, especially in elderly patients.

Objective Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent attacks of dyskinesia, in which movement of one body part produces involuntary movements of other body parts. Surround inhibition (SI), a mechanism for suppression of unwanted movements, could be deficient in these patients. To test this idea, we performed a transcranial magnetic stimulation (TMS) study in drug-naive patients with PKD. Methods TMS was set to be triggered by self-initiated flexion of the index finger at different intervals. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest. Normalized MEP amplitudes of the patients’ self-triggered TMS sessions at different intervals were compared to those of the controls. Results During index finger flexion, MEP amplitudes from the little finger muscle were unchanged in both the patients and normal subjects, however, post-movement MEP enhancement observed in the normal subjects was absent in patients with PKD. These results suggest that the functional operation of SI is itself preserved, but that post-movement excitation of surrounding muscles is deficient in PKD. Conclusions This finding may represent that the operation of SI is extended to the post-movement period, perhaps as a compensatory mechanism for preventing unwanted movement in surrounding muscles. Significance While many types of impaired inhibition have been described previously in PKD, this is the first possible example of increased inhibition.

Rapid eye movement sleep behavior disorder (RBD) is commonly accompanied in Parkinson disease (PD). However, the underlying mechanism linking RBD to PD remains unclear. We interviewed and examined 447 consecutive patients with PD to investigate factors associated with the presence of RBD in PD patients. Using the minimal diagnostic criteria for parasomnias provided in the International Classification of Sleep Disorders-Revised (ICSD-R), 164 patients (36.5%) were diagnosed with clinically probable RBD (cpRBD). PD patients with cpRBD were older, had a longer duration of PD, a more severe level of disability, a longer duration of antiparkinsonian medication, and a lower proportion of their Unified Parkinson Disease Rating Scale (UPDRS) scores accounted for by tremor than those without RBD. Multivariate and univariate logistic regression analyses revealed that patient age, PD symptom duration (and, accordingly, more severe motor disability), tremor score, and proportion of the UPDRS score accounted for by tremor were significant factors associated with the presence of RBD in PD patients. The results of the present study support previous observations that PD with RBD may result from a different underlying pattern of neurodegeneration than PD without RBD.

Objective: Surround inhibition (SI) in the motor system is an essential mechanism for the selective execution of desired movements. To investigate the relationship between the efficiency of SI operation in the motor system and handedness, we performed a transcranial magnetic stimulation (TMS) study in 10 healthy, right-handed volunteers. Methods: TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the adductor digiti minimi (ADM) and the flexor digitorum superficialis (FDS) muscles were compared between the dominant and non-dominant hands. Results: During index finger flexion, MEP amplitudes of the ADM in the dominant hand were suppressed but not in the non-dominant hand, while MEP amplitudes of the FDS were comparably enhanced in both hands. F-wave amplitudes of ADM were comparably enhanced during index finger flexion in both hands. Conclusion: These results suggest that the functional operation of SI in the motor system is more efficient in the dominant hand than the non-dominant hand. More efficient SI in the dominant hand could lead to greater dexterity in the dominant hand. Significance: Hemispheric asymmetry of SI might be able to serve as a neurophysiological proxy for handedness.

Although restless legs syndrome (RLS) commonly accompanies Parkinson disease (PD), the mechanism of RLS development in PD is still unclear. We investigated the prevalence of RLS in Korean patients with PD, and the possible contributing factors to the development of RLS in those patients. Four hundred forty-seven consecutive patients with PD were interviewed and examined. Among them, 73 patients (16.3%) were diagnosed with RLS. PD patients with RLS had a longer duration of PD symptoms, more severe PD disability, a greater degree of cognitive decline, and a longer duration of antiparkinson therapy than those without RLS. Multivariate logistic regression analysis revealed that the duration of antiparkinson therapy was the most significant factor contributing to the development of RLS in patients with PD. The present results support a higher prevalence of RLS in patients with PD and suggest that long-term antiparkinson therapy, rather than PD itself, may contribute to the development of RLS.

Objective Surround inhibition in the motor system is an essential mechanism for selective execution of desired movements. To evaluate the functional operation of surround inhibition in Parkinson disease, we performed a transcranial magnetic stimulation (TMS) study in the asymptomatic hands of hemiparkinsonism patients. Methods TMS was set to be triggered by self-initiated flexion of the index finger at different intervals from 3 to 2000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of control TMS at rest. Normalized MEP amplitudes of the patients’ self-triggered TMS sessions at different intervals were compared to those of the controls. Results During index finger flexion, MEP amplitudes from the little finger muscle were unchanged in normal subjects. However, they were enhanced in Parkinson patients, despite the absence of any motor disturbance. Conclusions These results suggest that the functional operation of surround inhibition is impaired in Parkinson disease. This disturbance may precede motor disturbance in Parkinson disease. Significance Impaired surround inhibition can be useful to detect preclinical parkinsonism.

Increasing evidence suggests an association between elevated serum aminotransferase level and the metabolic syndrome. However, the significance of relatively low levels of aminotransferase in relation to the metabolic syndrome has not been fully investigated in the general population. We investigated the association between serum amiontransferase level and the metabolic syndrome using data from a nationwide survey in Korea. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and metabolic conditions among 9771 participants aged 20 or more in the 1998 and 2001 Korean National Health and Nutrition Examination Surveys. Metabolic syndrome was defined according to NCEP-ATP III criteria with a modified waist circumference cutoff (men > 90 cm; women > 80 cm). Serum aminotransferase level, even within normal range, was associated with the metabolic syndrome independent of age, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios (95% CI) for an AST level of 20-29, 30-39, 40-49 and ≥ 50 IU/L were 1.10 (0.85-1.42), 1.37 (1.02-1.83), 1.62 (1.08-2.43), and 2.25 (1.47-3.44) in men, and 1.18 (0.99-1.41), 1.43 (1.29-1.83), 1.71 (1.09-2.68), and 2.14 (1.20-3.80) in women, respectively. Corresponding odds ratios for ALT levels were 1.27 (0.99-1.63), 1.69 (1.28-2.23), 2.17 (1.58-2.99), and 2.65 (1.96-3.58) in men, and 1.44 (1.22-1.70), 1.65 (1.26-2.15), 2.94 (1.93-4.47), and 2.25 (1.54-3.30) in women, respectively. In conclusion, elevated serum aminotransferase levels, even in the normal to near normal range, are associated with features of the metabolic syndrome.

Purpose Ulnar neuropathy at the cubital tunnel (UCT) is diagnosed on the basis of history, physical examination, and nerve conduction studies (NCSs); however, the wide spectrum of findings often makes the diagnosis difficult. The purpose of this study was to document the ultrasonographic differences in ulnar nerve size between patients with UCT and control subjects, and to correlate those differences with clinical examination findings and NCS abnormalities, thereby testing the validity of ultrasound (US) as an additional adjunct diagnostic modality for UCT. Methods Fifteen elbows in 14 patients with symptoms, clinical examination, and NCS findings consistent with UCT had US of the ulnar nerve. Patients were excluded if they had a history of polyneuropathy, acute trauma involving the upper extremity, previous trauma in the region of the elbow (including previous surgery), or brachial plexus injury. The control group consisted of 60 elbows from 30 normal volunteers that also had US. Maximal cross-sectional areas (CSAs) were measured and compared for the 2 groups and a correlation analysis was performed between nerve size and NCS findings. Results The average CSA of the ulnar nerve was 0.065 cm 2 in the control group, whereas in the UCT group it was 0.19 cm 2 , indicating a significant statistical difference in ulnar nerve size between the 2 groups. The Pearson correlation coefficient between motor nerve conduction velocity of the ulnar nerve and the CSA was 0.80. Conclusions High-resolution US is a noninvasive, safe, and reliable modality for imaging the ulnar nerve at the elbow and it may provide a valuable adjunct to NCS in the diagnosis of UCT. Type of study/level of evidence Diagnostic III.

AIM: To evaluate the association between the severity of liver steatosis and metabolic syndrome in apparently healthy Korean adults. METHODS: We examined 1 022 men and women, aged 30-79 years, who participated in a health screening test. A standard interview, anthropometrics, biochemical studies, and abdominal ultrasonography were conducted for each participant. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III, with a modification for the waist circumference cut-off level. The severity of liver steatosis was evaluated using liver ultrasonography, and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GT) levels were determined. RESULTS: Ultrasonographic liver steatosis was strongly associated with metabolic syndrome and common metabolic abnormalities. Compared with people without steatosis, people with mild, moderate, and severe steatosis had adjusted odds ratios for metabolic syndrome of 1.72 (95%CI, 1.01-2.94), 2.89 (1.75-4.76) and 3.53 (1.25-9.98) in men, and 2.86 (1.64-5.01), 3.19 (1.80-5.65) and 3.70 (0.82-16.73) in women, respectively. The serum AST level was not associated with metabolic syndrome. The serum ALT and γ-GT levels were significantly associated with metabolic syndrome in men but not in women. CONCLUSION: The occurrence of metabolic syndrome shows a stronger association with the severity of ultrasonographic steatosis than with the serum liver enzyme levels. The degree of fatty infiltration detected on ultrasonography can be used as an indicator of liver dysfunction attributable to metabolic abnormalities.

Various sensory symptoms and disturbed sensory perception are often observed in patients with idiopathic Parkinson's disease (PD). The basis of sensory disturbance in PD is unknown but possibly reflects a role for the basal ganglia in sensory processing. To investigate the relationship between the sensory dysfunction and dopaminergic deficiency in PD, we measured spatial discrimination using the Grating Orientation Task in 21 drug-naive patients with PD, before and after long-term antiparkinson therapy, and 25 age-matched healthy controls. The grating orientation threshold was significantly higher in patients (3.03 +/- 0.84) than controls (2.03 +/- 0.79). After 3 to 10 months of antiparkinson therapy, the grating orientation threshold was significantly lowered (2.66 +/- 0.84), although it was still higher than that in controls. Improvement in the patients' sensory function was significantly correlated with motor improvement (r = 0.44). These results suggest that sensory dysfunction in Parkinson's disease is related at least in part to the dopaminergic deficit.

Enteroviral CNS infection is common and its clinical course is usually benign. In immunocompromised patients, however, it can cause meningoencephalitis, presenting with altered mentality and seizure. We describe a previously healthy female patient with enteroviral meningoencephalitis who showed rapidly progressive aphasia. Examination of her cerebrospinal fluid (CSF) showed pleocytosis with lymphocyte dominance, elevated protein, and normal glucose, findings compatible with viral encephalitis. Fluid-attenuated inversion recovery (FLAIR) brain MRI showed hyperintensity in the left frontal and parietal cortices. Enterovirus in the CSF was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of the CSF. Although her neurological deficits had progressed to global aphasia, conservative management resulted in complete improvement within 3 months. This case provides unusual clinical manifestations and imaging findings in enteroviral encephalitis.

eISSN 2093-6338 Raf Kinase (BRAF) 유전자는 세포의 성장과 분화, 악성에 관여하 는 RAS/RAF/MEK/ERK 신호경로의 중요한 인자로서 흑색종, 대장 암, 갑상선암 등 다양한 종류의 종양 발생과 관련이 있다[1]. 미국 National Comprehensive Cancer Network (NCCN) [2]에서 는 미국 FDA 및 Clinical Laboratory Improvement Amendments (CLIA)에서 인증하는 검사실에서 BRAF V600E 유전자 돌연변이 가 확인된 경우 vemurafenib 치료를 권고하고 있다. 영국 National Health Service (NHS)의 의료기술평가 기관인 National Institute for Health and Clinical Excellence (NICE) [3]에서 2012년 보고한 권고지침에 따르면 vemurafenib은 적출이 불가능하거나 전이된

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders.

Purpose To investigate the influence of 2 phases of short interval intracortical inhibition (SICI) on the cortical silent period (SP). Materials and Methods Single- and paired-pulse transcranial magnetic stimulations (TMSs) at 1 and 2.5 ms interstimulus intervals (ISIs) were applied to the left motor cortex in 12 healthy subjects while their right hand muscles were moderately activated. Conditioning stimulation intensity was 90% of the active motor threshold (AMT). Test stimulation intensities were 120, 140, 160, 180, 200, 220, 240, 260% of the AMT and at 100% of the maximal stimulator output, the order of which was arranged randomly. The rectified electromyography area of motor evoked potential (MEP) and duration of the SP were measured off-line using a computerized program. Results At high-test stimulation intensities, MEP areas were saturated in both single- and paired-pulse stimulations, except that saturated MEPs were smaller for the paired-pulse TMS at 1 ms ISI than for the other conditions. As the test stimulation intensity increased, SP was progressively prolonged in both single- and paired-pulse stimulations but was shorter in paired-pulse than single-pulse TMS. Overall, the ratio of SP duration/MEP area was comparable between single- and paired-pulse TMS except for the paired-pulse TMS at 1 ms ISI with a test stimulation intensity at 140 - 180% of the AMT, in which the ratio was significantly higher than in the single pulse TMS. Conclusion These results suggest that 2 phases of SICI modulate MEP saturation and SP duration differently and provide additional evidence supporting the view that 2 phases of SICI are mediated by different inhibitory mechanisms.

Objectives The delayed separation of whole blood can influence the concentrations of circulating blood components, including metabolites and cytokines. The aim of this study was to determine whether clinical-biochemistry analytes can be used to assess the delayed separation of whole blood. Methods We investigated the plasma and serum concentrations of five clinical-biochemistry analytes and free hemoglobin when the centrifugation of whole blood stored at 4°C or room temperature was delayed for 4 hours, 6 hours, 24 hours, or 48 hours, and compared the values with those of matched samples that had been centrifuged within 2 hours after whole-blood collection. Results The inorganic phosphorus (IP) levels in the plasma and serum samples were elevated ≥ 1.5-fold when whole-blood centrifugation was delayed at room temperature for 48 hours. Furthermore, the IP levels in the plasma samples showed excellent assessment accuracy [area under the receiver-operating-characteristic curve (AUC) > 0.9] after a 48-hour delay in whole-blood separation, and high sensitivity (100%) and specificity (95%) at an optimal cutoff point. The IP levels in the serum samples also exhibited good assessment accuracy (AUC > 0.8), and high sensitivity (81%) and specificity (100%). The potassium (K + ) levels were elevated 1.4-fold in the serum samples following a 48-hour delay in whole-blood separation. The K + levels showed excellent assessment accuracy (AUC > 0.9) following a 48-hour delay in whole-blood separation, and high sensitivity (95%) and specificity (91%) at an optimal cutoff point. Conclusion Our study showed that the IP and K + levels in the plasma or serum samples could be considered as putative indicators to determine whether whole-blood separation had been delayed for extended periods.

Mesial temporal sclerosis (MTS) is a well-recognized cause of intractable epilepsy; however, coexistence with focal cortical dysplasia (FCD) is less common. Middle fossa epidermoid cysts are rare and may involve the temporal lobe. Most epidermoids are clinically silent, slow-growing, and seldom associated with overt symptomatology, including seizures. We describe a patient with multiple comorbidities including left MTS and a large epidermoid cyst involving the left quadrigeminal plate cistern compressing upon the cerebellar vermis and tail of the left hippocampus, resulting in refractory left temporal lobe epilepsy. The patient underwent left anterior temporal lobectomy. The surgical pathology demonstrated a third pathological finding of left temporal FCD type Ia. The patient has been seizure-free since the surgery. This case provides additional information with regard to the understanding of epileptogenicity and surgical planning in patients with MTS and epidermoid cysts.

Background: Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. Case presentation: A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. Conclusion: We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.