An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report.

BACKGROUND Alcohol abuse inhibits the ability of the liver to release glucose into the bloodstream, primarily by inhibiting gluconeogenesis, so chronic alcohol abusers exhibit hypoglycemia after drinking alcohol without eating; this is called alcohol-induced hypoglycemia. Central adrenal insufficiency (AI) is characterized by cortisol deficiency due to a lack of adrenocorticotropic hormone. It is challenging to diagnose central AI, as it usually presents with nonspecific symptoms, such as asthenia, anorexia, and a tendency toward hypoglycemia. Here, we report a rare case of central AI that presented with AI symptoms shortly after an alcohol-induced hypoglycemic coma. CASE REPORT An 81-year-old Japanese man who had been a moderate drinker for >40 years developed a hypoglycemic coma after consuming a large amount of sake (alcohol, 80 g) without eating. After the hypoglycemia was treated with a glucose infusion, he rapidly recovered consciousness. After stopping alcohol consumption and following a balanced diet, he had normal plasma glucose levels. However, 1 week later, he developed asthenia and anorexia. The endocrinological investigation results indicated central AI. He was started on oral hydrocortisone (15 mg/day), which relieved his AI symptoms. CONCLUSIONS Cases of central AI associated with alcohol-induced hypoglycemic attacks have been reported. Our patient developed AI symptoms following an alcohol-induced hypoglycemic attack. His alcohol-induced hypoglycemic attack likely occurred in combination with a developing cortisol deficiency. This case highlights the importance of considering central AI in chronic alcohol abusers presenting with nonspecific symptoms, including asthenia and anorexia, especially when patients have previously experienced alcohol-induced hypoglycemic attacks.

Hypoglycemic Hemiplegia Associated with Reversible Narrowing of the Contralateral Middle Cerebral Artery in a Patient with Adrenal Insufficiency.

A 56-year-old man with a 2.5-month history of anorexia developed sweating, weakness, and left hemiplegia and hemispatial neglect. Brain magnetic resonance imaging detected no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery (MCA). The focal neurological signs and narrowing of the MCA resolved after detection and correction of hypoglycemia. Endocrinological examinations indicated adrenal insufficiency. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, although the mechanisms involved remain unknown. Combined hypoglycemia and decreased MCA blood flow associated with vasospasm probably induced regionally severe neuroglycopenia with ischemia, which presented as focal neurological symptoms.

Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as the Predominant Manifestation of Adrenal Insufficiency.

A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after the initiation of corticosteroid replacement therapy. To our knowledge, this is the first reported case of adrenal insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should consider reversible non-parkinsonian bradykinesia associated with frontal lobe dysfunction as an unusual manifestation of adrenal insufficiency.

Generalized Status Epilepticus in a Patient with Acute-onset Type 1 Diabetes Mellitus Associated with Severe Kidney Dysfunction: A Case Report and Literature Review.

A 65-year-old Japanese man with advanced chronic kidney disease (CKD) developed acute-onset type 1 diabetes mellitus (T1D) that was associated with severe acute kidney injury and was manifested by generalized tonic-clonic status epilepticus. His seizures resolved without recurrence after correcting the diabetic ketoacidosis. Although hyperglycemia is an important cause of acute symptomatic seizure (ASS), patients with ketotic hyperglycemia develop ASS less frequently. In this T1D case with CKD, severe hyperglycemia in conjunction with other metabolic insults, such as uremia, hyponatremia, and hypocalcemia, probably provoked his seizure despite the severe ketonemia.

Visualization of the Intimal Flap in Intracranial Arterial Dissection Using High-Resolution 3T MRI.

BACKGROUND AND PURPOSE: Presence of an intimal flap is a critical imaging finding in diagnosing intracranial artery dissection (ICAD). Recent reports showed that high-resolution magnetic resonance imaging (MRI) was better at identifying intimal flaps as compared with routine MRI techniques used in clinical settings. However, no current standardized sequence for high-resolution MRI without gadolinium enhancement produces images of satisfactory quality with clinically tolerable scanning times. This study evaluated a nonenhanced high-resolution fast spin echo (HR-FSE) MRI sequence for visualizing intimal flaps in patients with ICAD. SUBJECTS AND METHODS: Three patients with ICAD underwent plain MRI examination using a 2-dimensional T2-weighted FSE imaging sequence optimized for our 3T system (in-plane pixel size, .23 mm × .23 mm; slice thickness 3 mm with no interslice gap), as well as scanning with conventional modalities, including CT angiography, magnetic resonance angiography, and digital subtraction angiography. We assessed whether these imaging methods could visualize an intimal flap and/or double lumen sign in the participants and compared the results between HR-FSE and the other modalities. RESULTS: HR-FSE images clearly showed intimal flaps and double lumen signs in all 3 patients, whereas the conventional modalities identified a double lumen sign in only 2 of the 3 patients. CONCLUSIONS: The present method of optimized HR-FSE imaging with a 3T system improved visualization of intimal flaps and should thus be considered for assessing patients with suspected ICAD that cannot be definitively diagnosed by conventional imaging modalities.

Laryngeal stridor in multiple system atrophy: Clinicopathological features and causal hypotheses.

Laryngeal stridor is recognized as a characteristic clinical manifestation in patients with multiple system atrophy (MSA). However, the pathogenic mechanisms underlying this symptom are controversial. Neurogenic atrophy of the posterior cricoarytenoid muscle has been identified in cases of MSA, suggesting that laryngeal abductor weakness contributes to laryngeal stridor. However, dystonia in the laryngeal adductor muscles has also been reported to cause laryngeal stridor. Depletion of serotonergic neurons in the medullary raphe nuclei, which exert tonic drive to activate the posterior cricoarytenoid muscle, has recently been identified in MSA cases. This adds weight to the possibility that laryngeal abductor weakness underlies laryngeal stridor in MSA. Continuous positive airway pressure therapy is currently used in the treatment of laryngeal stridor, but should be used with caution in patients showing contraindications. Current knowledge of the clinical and neuropathological features of laryngeal stridor is summarized in this paper, and the hypothesized causes and possible therapeutic options for this symptom are discussed.

Diffuse brain abnormalities in myotonic dystrophy type 1 detected by 3.0 T proton magnetic resonance spectroscopy.

Patients with myotonic dystrophy type 1 (DM1) (n = 14) were compared with healthy controls (n = 13) using 3.0 T proton magnetic resonance spectroscopy ((1)H-MRS) to investigate brain pathophysiology. (1)H-MRS imaging revealed reduced N-acetylaspartate to creatine ratio (NAA/Cr) in multiple brain regions (average 24%), suggesting diffuse brain abnormalities among patients with DM1. Single-voxel (1)H-MRS among patients with DM1 showed (1) reduced NAA in both the frontal cortex (23%) and frontal white matter (31%) and unaltered myo-inositol, suggesting neuronal abnormalities without significant gliosis; and (2) elevated glutamine in the frontal cortex (36%) and reduced glutamate in the frontal white matter (20%) among patients with DM1, suggesting abnormalities in the glutamatergic system in the brain of patients with DM1. We consider that these results reflect brain abnormalities that cannot be detected by neuropathological assessment in patients with DM1.

Apparent diffusion coefficients distinguish amyotrophic lateral sclerosis from cervical spondylotic myelopathy.

OBJECTIVE: Fifty percent of patients with amyotrophic lateral sclerosis (ALS) have cervical spondylotic myelopathy (CSM) as a complication. Because patients with ALS do not develop bulbar signs and symptoms at onset, differentiating them from patients with CSM is sometimes difficult. We aimed to determine whether the apparent diffusion coefficients (ADCs) of intracranial corticospinal tracts can be used to distinguish between patients with ALS and those with CSM. METHODS: We evaluated 19 consecutive patients with ALS who did not have CSM by cervical MRI, 16 patients with CSM, and 11 healthy controls. We examined the mean ADCs in the precentral gyrus, the corona radiata, the posterior limbs of the internal capsule (PLIC), and the cerebral peduncle by 3T magnetic resonance imaging (MRI). The mean ADCs in the intracranial corticospinal tracts in patients with ALS were compared with those in patients with CSM. RESULTS: The mean ADCs in the intracranial corticospinal tracts in patients with ALS were compared with those in patients with CSM (p<0.05). Additionally, the mean ADCs in the precentral gyrus, the PLIC, and the cerebral peduncle in the patients with ALS, including the patients who were initially diagnosed as having clinically possible ALS on the basis of the revised El Escorial criteria and did not develop bulbar symptoms at onset, were also higher than those in patients with CSM (p<0.05). CONCLUSIONS: Elevated ADCs in the intracranial corticospinal tracts might be useful for distinguishing ALS from CSM in the early stage of the disease.

Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: a cost-effectiveness analysis.

BACKGROUND: Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease. AIM: To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD. METHODS: A decision analysis model is constructed to compare, over a time horizon of 1year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-α therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results. RESULTS: The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750. CONCLUSIONS: Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness.

Association of nitrogen compounds in drinking water with incidence of esophageal squamous cell carcinoma in Shexian, China.

The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth most common malignancy worldwide, is highest in China. The purpose of this study was to investigate the association between nitrogen compounds in drinking water with the incidence of ESCC by geographical spatial analysis. The incidence of ESCC is high in Shexian county, China, and environmental factors, particularly nitrogen-contaminated drinking water, are the main suspected risk factors. This study focuses on three nitrogen compounds in drinking water, namely, nitrates, nitrites, and ammonia, all of which are derived mainly from domestic garbage and agricultural fertilizer. The study surveyed 48 villages in the Shexian area with a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer subjects). Hot-spot analysis was used to identify spatial clusters with a high incidence of ESCC and a high concentration of nitrogen compounds. Logistic regression analysis was used to detect risk factors for ESCC incidence. Most areas with high concentrations of nitrate nitrogen in drinking water had a high incidence of ESCC. Correlation analysis revealed a significant positive relationship between nitrate concentration and ESCC (P = 0.01). Logistic regression analysis also confirmed that nitrate nitrogen has a significantly higher odds ratio. The results indicate that nitrate nitrogen is associated with ESCC incidence in Shexian county. In conclusion, high concentrations of nitrate nitrogen in drinking water may be a significant risk factor for the incidence of ESCC.

Brainstem metabolites in multiple system atrophy of cerebellar type: 3.0-T magnetic resonance spectroscopy study.

BACKGROUND: The aim of this study was to find biomarkers of disease severity in multiple system atrophy of cerebellar type by imaging disease specific regions using proton magnetic resonance spectroscopy on a 3.0 T system. METHODS: We performed proton magnetic resonance spectroscopy separately in the pons and medulla on 12 multiple system atrophy of cerebellar type patients and 12 age and gender matched control subjects. The metabolite concentrations were estimated from single-voxel proton magnetic resonance spectra measured by point resolved spectroscopy, which were then correlated with clinical severity using Part I, II, and IV of the unified multiple system atrophy rating scale. RESULTS: Proton magnetic resonance spectroscopy showed that myo-inositol concentrations in both the pons and medulla were significantly higher in multiple system atrophy of cerebellar type patients compared to those of the control subjects (P < 0.05). By contrast, total N-acetylaspartate (the sum of N-acetylaspartate and N-acetylaspartylglutamate) and total choline compounds concentrations in both the pons and medulla were significantly lower in multiple system atrophy of cerebellar type patients compared to control subjects (P < 0.05). Creatine concentration in the pons was significantly higher in multiple system atrophy of cerebellar type patients compared to the control subjects (P < 0.05). Furthermore, a significant correlation was found between the myo-inositol/creatine ratio in the pons and clinical severity, defined by the sum score of unified multiple system atrophy rating scale (I+II+IV) (r = 0.76, P < 0.01). CONCLUSION: Proton magnetic resonance spectroscopy, in conjunction with a 3.0 T system, can be feasible to detect part of pathological changes in the brainstem, such as gliosis and neuronal cell loss, and the metabolites can be used as biomarkers of clinical severity in multiple system atrophy of cerebellar type patients.

A stochastic model of neuronal growth cone guidance regulated by multiple sensors.

Neuronal growth cones migrate directionally under the control of axon guidance molecules, thereby forming synapses in the developing brain. The signal transduction system by which a growth cone detects surrounding guidance molecules, analyzes the detected signals, and then determines the overall behavior remains undetermined. In this study, we describe a novel stochastic model of this behavior that utilizes multiple sensors on filopodia to respond to guidance molecules. Overall growth cone behavior is determined by using only the concentration gradients of guidance molecules in the immediate vicinity of each sensor. The detected signal at each sensor, which is treated as a vector quantity, is sent to the growth cone center and then integrated to determine axonal growth in the next step by means of a simple vector operation. We compared the results of computer simulations of axonal growth with observations of actual axonal growth from co-culture experiments using olfactory bulb and septum. The probabilistic distributions of axonal growth generated by the computer simulation were consistent with those obtained from the culture experiments, indicating that our model accurately simulates growth cone behavior. We believe that this model will be useful for elucidating the as yet unknown mechanisms responsible for axonal growth in vivo.

Tract-by-tract morphometric and diffusivity analyses in vivo of spinocerebellar degeneration.

BACKGROUND AND PURPOSE: Three-dimensional anisotropy contrast (3DAC) based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) sequence on a 3.0 T system is a new magnetic resonance imaging technique capable of providing images with significantly high anatomical resolution. The purpose of this study was to confirm whether this technique can characterize the degenerative processes in the brainstem of patients with spinocerebellar degeneration (SCD). METHODS: 3DAC images of 13 patients with multiple system atrophy with predominant cerebellar symptoms (MSA-C) and seven International Cooperative Ataxia Rating Scale (ICARS) score-matched patients with Machado-Joseph disease (MJD) were created using a diffusion-weighted PROPELLER sequence on a 3.0T system. The section of the middle pons was chosen for morphometric and diffusivity analyses. RESULTS: The above analyses showed that atrophy and increased diffusivity of the ventral portion of the pons indicated MSA-C, whereas atrophy and increased diffusivity of the pontine tegmentum indicated MJD. Furthermore, ICARS scores significantly correlated with both the severities of the pontine atrophy and the mean diffusivity values of the ventral pontocerebellar tracts. CONCLUSIONS: This study demonstrated that 3DAC PROPELLER on a 3.0T system enables in vivo "tract by tract" quantitative analysis of pontine degeneration in SCD.

Cost-effectiveness of the national screening program for hepatitis C virus in the general population and the high-risk groups.

In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and--749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.

Serial assessments of delayed encephalopathy after carbon monoxide poisoning using magnetic resonance spectroscopy and diffusion tensor imaging on 3.0T system.

To elucidate the still unclear mechanism of delayed encephalopathy after carbon monoxide (CO) poisoning, we serially performed single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion tensor imaging (DTI) on a 3.0T system and intelligence tests in 2 patients, while they were undergoing hyperbaric oxygenation therapy. The chronological changes in (1)H-MRS- and DTI-derived parameters indicated the following: (1) White matter demyelination, aerobic metabolism inhibition, and cytotoxic edema persisted for at least 3 months even after starting the hyperbaric oxygenation therapy; (2) the axonal function and structural integrity of the white matter were initially severely impaired and then gradually and partially improved for 5 months, showing changes similar to those in the scores of the intelligence tests. The results demonstrated that brain damage after CO poisoning may persist longer than expected, and that the (1)H-MRS- and DTI-derived parameters are good indicators of the clinical progress of a patient. The combination of (1)H-MRS and DTI on a 3.0T system is useful for monitoring the changes in brain damage and the clinical symptoms of patients with delayed encephalopathy after CO poisoning.

Cell-oriented analysis in vivo using diffusion tensor imaging for normal-appearing brain tissue in multiple sclerosis.

There have been several methods proposed so far using diffusion tensor imaging (DTI) for the assessment of normal-appearing brain tissue (NABT) injury in multiple sclerosis (MS). However, for these methods, the analyses of the NABT injury at the cellular level, wherein histological examinations can be used, still present challenging problems. We developed a method of segregating NABT into the following anatomical structures using lambda chart analysis associated with a two-dimensional Gaussian deconvolution of diffusion characteristic functions: 1) structures primarily composed of small neurons and glia; 2) structures primarily composed of large neurons; 3) structures primarily composed of short axons; and 4) structures primarily composed of long axons. Each segregated structure that had a distinctive diffusion characteristic was subjected to the statistical inference of DTI-derived parameters for 14 patients with conventional relapsing-remitting MS (RRMS) and 20 age-matched healthy volunteers. In all of the structures, the trace values were significantly higher and the fractional anisotropy values were significantly lower in the RRMS patients than in the healthy volunteers. Furthermore, the volume fractions of the structures primarily composed of short axons markedly decreased, whereas those of the structures primarily composed of small neurons and glia markedly increased. These results suggest that axonal loss and glial proliferation predominantly occurred in the subcortical white matter and adjacent deep cortical layer, namely, the juxtacortical region. This cell-oriented analysis of NABT injury using DTI confirmed in vivo the histological observation that the juxtacortical region is the most vulnerable site in MS.

Daytime hypoxemia, sleep-disordered breathing, and laryngopharyngeal findings in multiple system atrophy.

BACKGROUND: The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne-Stokes respiration; or an impaired hypoxemic ventilatory response. OBJECTIVE: To investigate the mechanism of sleep-disordered breathing in multiple system atrophy (MSA). DESIGN: We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia. RESULTS: A decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration (P = .045 and .046, respectively). Polysomnography demonstrated Cheyne-Stokes respiration in 3 (15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 (14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 (45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 (55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid. CONCLUSIONS: We observed daytime hypoxemia with an increased alveolar-arterial oxygen gradient, Cheyne-Stokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.

Multiplex families with multiple system atrophy.

BACKGROUND: Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance. OBJECTIVE: To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects. DESIGN: Clinical and genetic study. SETTING: Four departments of neurology in Japan. Patients Eight patients in 4 families with parkinsonism, cerebellar ataxia, and autonomic failure with age at onset ranging from 58 to 72 years. Two siblings in each family were affected with these conditions. MAIN OUTCOME MEASURES: Clinical evaluation was performed according to criteria by Gilman et al. Trinucleotide repeat expansion in the responsible genes for the spinocerebellar ataxia (SCA) series and for dentatorubral-pallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the alpha-synuclein gene was performed. RESULTS: Consanguineous marriage was observed in 1 of 4 families. Among 8 patients, 1 had definite MSA, 5 had probable MSA, and 2 had possible MSA. The most frequent phenotype was MSA with predominant parkinsonism, observed in 5 patients. Six patients showed pontine atrophy with cross sign or slitlike signal change at the posterolateral putaminal margin or both on brain magnetic resonance imaging. Possibilities of hereditary ataxias, including SCA1 (ataxin 1, ATXN1), SCA2 (ATXN2), Machado-Joseph disease/SCA3 (ATXN1), SCA6 (ATXN1), SCA7 (ATXN7), SCA12 (protein phosphatase 2, regulatory subunit B, beta isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the alpha-synuclein gene were found. CONCLUSIONS: Findings in these multiplex families suggest the presence of familial MSA with autosomal recessive inheritance and a genetic predisposition to MSA. Molecular genetic approaches focusing on familial MSA are expected to provide clues to the pathogenesis of MSA.

A possible variant of neuro-Behçet disease presenting chronic progressive ataxia without mucocutaneo-ocular symptoms.

Behçet disease (BD) is a chronic relapsing multisystem disorder of unknown etiology, which preferentially affects the oral and genital mucous membranes, skin, and eyes. Neurological involvement is one of the most serious manifestations of BD, known as neuro-Behçet disease (NBD). We here describe clinical, radiological, and neuropathological findings for two patients with a possible variant of NBD, who manifested progressive ataxia in the absence of mucocutaneo-ocular signs characteristic for BD. Both patients presented a slowly progressive cerebellar phenotype, accompanied by behavioral changes and sphincter disturbance. Brain MRI scan revealed mild atrophy in pons and cerebellum. Both patients showed a mild CSF pleocytosis, and were positive for HLA-B51. The post-mortem examination performed in one patient, showed widespread foci of chronic encephalitis, consistent with the diagnosis of NBD. Steroid pulse therapy was effective in one patient. Identifying the progressive ataxia phenotype of NBD without mucocutaneo-ocular symptoms is important, because these patients may benefit from early steroid therapy.