Combined genetic defects in a child with ischemic stroke: case report

A 10-year-old Turkish boy was admitted with mild right spastic hermiplegia. First, he experienced sudden numbness and weakness in the right extremities at the age of 2 years and was diagnosed with right hemiparesis. His parents were generally healthy and non-consanguineous. His mother suffered from deep vein thrombosis of the left lower extremity during pregnancy and had recurrent fetal loss. At the age of 10 years, a thrombophilia marker examination revealed that plasma-free protein S was 49.3% (normal range = 70-123%), and factor VIII level was found to be 470 IU/dL (normal = 150 IU/dL). The patient and his two siblings were found to be heterozygous for factor V Leiden mutation. His mother was also heterozygous for factor V Leiden mutation and had protein S deficiency. A combination of protein S deficiency, factor V Leiden mutation, and a high level of factor VIII was detected in our patient. After his first attack at the age of 2 years, in spite of no prophylaxis, he did not experience any other ischemic insult. To our knowledge, this is the first patient with these combinations of genetic defects and ischemic stroke to be reported in the literature.     

A case of polymyositis with repeated dysphagia and muscle weakness associated with peculiar findings of skin

A case of polymyositis with repeated dysphagia and muscle weakness associated with peculiar findings of skin was reported. The patient was a 67-year-old man. His birth and development was normal. There was no family history of neuromuscular disease. On 26th March 1987 he was admitted to a hospital because of dysarthria and dysphagia after fever and diagnosed as having viral myositis. His conditions improved spontaneously with bed rest and he left hospital on 14th April. On 23rd April he had chill and sore throat with fever. On 27th he was admitted to the same hospital because of dysarthria and muscle weakness of the proximal portion of the upper limbs. These symptoms also improved with bed rest. He had repeated these symptoms several times and then he was admitted to our hospital on 12th June. On examination he showed the skin pigmentation under the right eye and the eruption in the back of hands and the buttocks. Muscle weakness was observed in the proximal portion of the upper limbs and the neck flexor. Laboratory tests in admission were as follows: sGOT 49 mU/ml, sGPT 104 mU/ml, LDH 1064 mU/ml, CPK 565 mM/ml, aldolase 25.2 IU/1/37 degrees C. Electromyography showed the typical myogenic changes and biopsy of left biceps brachii revealed inflammatory cells in the muscle fiber which are specific to polymyositis. Immuno-histochemical study is performed to analyse the subpopulation of mononuclear cells in biopsied muscle and skin. Mononuclear cells infiltrated into perimysium, endomysium and epidermis were positive for T11 and T8, but less positive for T4, B1 and Leu11. On the basis of these findings he was diagnosed as having "polymyositis syndrome".     

Hypothyroid myopathy caused by interferon-alpha therapy for chronic hepatitis C]

We reported a rare case with hypothyroid myopathy after interferon-alpha (IFN-alpha) therapy. A 59-year-old man complained of his weakness in proximal part of upper and lower extremities which started at 1 month and progressed during 6 months after IFN-alpha therapy for chronic hepatitis C, but he did not complain of any other symptoms. Blood chemistry showed an elevated level of CK (1,843 IU/l; normal range 43-170 IU/l) and increased myoglobin (250 ng/ml; normal range < 60 ng/ml). Thyroid function tests revealed an elevated level of TSH (148.7 microIU/ml; normal range, 0.4-4.1 microIU/ml), and decreased levels of free T3 (0.56 pg/ml; normal range, 2.27-3.90 pg/ml) and free T4 (0.24 ng/ml; normal range, 0.95-1.74 ng/ml). Blocking type TSH receptor antibody titer was elevated (75.4%; normal range < 15%) while other types of antithyroid antibody were not detected in his serum. Muscle biopsy from his quadriceps femoris muscle showed non-specific mild myopathic changes. His weakness was completely ameliorated and serum CK levels were normalized by thyroid hormone administration alone, confirming the diagnosis of hypothyroid myopathy. However, even after total amelioration of his hypothyroidism, blocking type TSH receptor antibody titer remained elevated. These findings may suggest that IFN-alpha fostered an autoreactivity arising from HCV infection to cause the autoimmune thyroid disease.     

A case of skeletal muscle type very-long-chain-acyl CoA dehydrogenase(VLCAD) deficiency with repeated rhabdomyolysis]

We experienced a 24-year-old male patient with myalgia and myoglobuinuria followed by severe exercise from childhood. In 18 years old, he had severe myaglia after a long time-night trip by bus. He was diagnosed as acute renal failure induced by rhabdomyolysis and treated with hemodialysis. In 24 years old, he was admitted to our hospital because of repeated rhabdomyolysis. We performed muscle biopsy from right quadriceps femoris, however histological and immunohistochemistological studies were normal. Ischemic forearm exercise test showed the elevation of lactic acid in serum. Therefore, we performed the analysis of acylcarnitine in serum, and the measurement of enzyme in beta-oxidation in muscle and white blood cells. These showed the lack of very-long-chain-acyl coA dehydrogenase (VLCAD) activity. He was diagnosed as skeletal muscle type VLCAD deficiency. Under the guidance of high carbohydrate and low fat diet, creatine kinase was controlled around 400 IU/l. VLCAD deficiency is important to make a differential diagnosis of young cases with recurrent elevation of creatine kinase.     

The role of prosody in a case of foreign accent syndrome (FAS)

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. The symptomotology, functional bases, and neural substrates of this disorder are still being elucidated. In this case study, acoustic analyses were performed on the speech of a 46-year old monolingual female who presented with FAS of unknown aetiology. The patient had a pseudo-accent frequently described as 'Swedish' or 'Eastern European'. Stop consonant VOT, consonant burst spectra and duration, vowel durations, formant frequencies, and trajectories were analysed, along with prosodic cues for lexical stress assignment and sentence-level intonation. Results indicated VOT values were generally preserved, while there was a strong tendency to realize the English alveolar flap as a full stop, and to produce flaps that had greater-than-normal closure durations. The spectral properties of the patient's vowels resembled those of normal talkers (with the possible exceptions of decreased F1 values for /i/ and slight differences in formant dynamics for /u/, /o/, /i/, and /epsilon/). However, vowel durations were relatively long, contributing to exaggerated tense/lax contrasts. Token-to-token variability in vowel production was slightly higher than normal for duration, but not for formant frequency values. Lexical stress assignment was inaccurate and highly variable (with similar problems noted for non-speech materials), and sentence level intonation showed occasional deviations from typical American English patterns. For this patient, an underlying timing/rhythm difficulty appeared responsible for the range of segmental and suprasegmental changes leading to the impression of a foreign accent.     

Recurrent attacks of fear and visual hallucinations in a child

The case of a 7-year-old boy suffering from recurrent nocturnal and occasional daytime attacks with intense fear and complex visual hallucinations is presented. His state was otherwise normal, as were routine electroencephalographic (EEG) and magnetic resonance imaging (MRI) investigations in the past. Several differential diagnoses such as panic disorder, pavor nocturnus, and nightmares were considered but could not be definitely established or excluded. Since the attacks appeared after the divorce of his parents, an adjustment disorder was suspected, and the patient received psychotherapy for more than 2 years without an effect on the attacks. Only when long-term video-EEG recorded two typical attacks with left temporal ictal seizure patterns was focal epilepsy diagnosed and successfully treated with antiepileptic medication. A suspected origin of seizures in the amygdala was supported by a high-resolution MRI showing a cortical dysplasia extending from the left anteromedial temporal lobe to the amygdala. The case exemplifies difficulties in the differential diagnosis of panic-like attacks and underlines the value of long-term video-EEG, which may be necessary to establish the correct diagnosis and to prevent ineffective therapeutical approaches.     

A case of Hopkins syndrome with onset at puberty]

The patient was a 15-year-old man who developed weakness of left leg 6 days after an acute asthmatic attack. Neurological examination revealed severe muscle weakness and atrophy at L5-S1 level and mild muscle weakness and atrophy at L2-4 level in the left leg. Deep tendon reflexes were normal in the upper limbs and slightly brisk in the lower limbs except for absence of Achilles tendon reflex on the left. His sensation was normal. Needle EMG revealed neurogenic changes in both the left (L2-S1) and right (L2-4) leg muscles. Motor nerve conduction study of the left tibial and peroneal nerves revealed a marked reduction of amplitude and mild reduction of MCV. F-wave was not evoked in either nerves. Sensory nerve conduction study of the left sural nerve was normal. The titers of anti-viral antibodies in the paired sera showed no significant changes in any viruses examined including echovirus, enterovirus, coxsackievirus and poliovirus type 1, 2 and 3. The serum IgE was elevated (1,300 IU/ml) and mite antigen-specific IgE was strongly positive. Spinal cord MRI revealed no abnormality in either thoracic or lumbar spinal cord. This patient was diagnosed as a rare case of Hopkins syndrome with onset at puberty.     

An adult case of congenital fiber type disproportion (CFTD) with cardiomyopathy]

A 30 year-old man with CFTD was reported. He had normal motor milestone during infancy but had been poor at sports. At 28, he experienced exertional and nocturnal dyspnea and had been diagnosed as having dilated cardiomyopathy. At 29, a cardiac pace-maker was implanted because of the complete atrio-ventricular block. Around that time, he began to notice limb muscle weakness. Examination at 30 showed mild diffuse muscle atrophy and weakness at the torso and limbs. No dysmorphic features or joint contractures were noted. His serum CK was normal. A histochemical study of his muscle biopsy showed type 1 fiber predominancy (64.6%) and that the mean diameter of type 1 fibers was smaller than that of type 2 by 14.6% (36.9 microm vs. 42.3 microm). Results of immunostaining of dystrophin, emerin, laminA/C, alpha, beta, gamma, delta-sarcoglycan or dysferlin were normal. He was diagnosed as having CFTD because there were no histochemical abnormalities which characterize other congenital myopathies except for the type 1 predominancy and atrophy.     

Guillain-Barré syndrome associated with Salmonella paratyphi A

A 31-year-old Nepali man was admitted to the intensive care unit with a 3-day history of fever associated with four-limb weakness, followed by difficulty in swallowing. The patient came from Nepal 20 days before admission. On examination the patient was conscious and appeared ill, with a temperature of 38.0 degrees C. His four limbs were weak (grades 2-3) and he was areflexic with mild facial weakness and absent gag reflex. Brain CT and MRI were normal. Cerebrospinal fluid analysis showed high protein. A neurophysiologic study showed data consistent with motor axonal polyradiculopathy. The patient was diagnosed with Guillain-Barré syndrome (GBS), and intravenous immunoglobulin (0.4 g/kg day for 5 days) was administered. On the third hospitalization day, the patient developed respiratory failure for which he was intubated and mechanically ventilated. On the same day, blood samples grew Salmonella paratyphi A (S. paratyphi A), which was sensitive to ceftriaxone. The patient was then diagnosed with GBS associated with S. paratyphi A, and treated with ceftriaxon (2 g administered intravenously, daily for 10 days). On the eleventh hospitalization day the patient was weaned from ventilator and extubated successfully. Subsequently, the patient improved, his fever subsided, and he regained muscle power satisfactorily.     

The role of prosody in a case of foreign accent syndrome (FAS)

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. The symptomotology, functional bases, and neural substrates of this disorder are still being elucidated. In this case study, acoustic analyses were performed on the speech of a 46‐year old monolingual female who presented with FAS of unknown aetiology. The patient had a pseudo‐accent frequently described as ‘Swedish’ or ‘Eastern European’. Stop consonant VOT, consonant burst spectra and duration, vowel durations, formant frequencies, and trajectories were analysed, along with prosodic cues for lexical stress assignment and sentence‐level intonation. Results indicated VOT values were generally preserved, while there was a strong tendency to realize the English alveolar flap as a full stop, and to produce flaps that had greater‐than‐normal closure durations. The spectral properties of the patient's vowels resembled those of normal talkers (with the possible exceptions of decreased F1 values for /i/ and slight differences in formant dynamics for /u/, /o/, /i/, and /?/). However, vowel durations were relatively long, contributing to exaggerated tense/lax contrasts. Token‐to‐token variability in vowel production was slightly higher than normal for duration, but not for formant frequency values. Lexical stress assignment was inaccurate and highly variable (with similar problems noted for non‐speech materials), and sentence level intonation showed occasional deviations from typical American English patterns. For this patient, an underlying timing/rhythm difficulty appeared responsible for the range of segmental and suprasegmental changes leading to the impression of a foreign accent.     

Connatal type of Pelizaeus-Merzbacher disease: a case report

Pelizaeus-Merzbacher disease (PMD) is a hereditary disorder with myelin dysplasia in the central nervous system. The connatal type is a more severe form compared to the classical type and shows developmental arrest or deterioration, nystagmus, spasticity, and/or convulsions in the neonatal period. A 1 1/4-year-old Japanese boy diagnosed as connatal type PMD is reported here. Soon after his birth, he demonstrated horizontal and rotatory nystagmus and opisthotonic posture. At the age of 10 months, he had difficulty in feeding. At the age of 1 year, he presented more severe opisthotonic posture and frequent vomiting. He showed deterioration in gross motor development. His chromosome analysis showed a normal male karyotype. Electroencephalogram did not show a sleep spindle. Auditory evoked brainstem responses (ABR) showed only wave I on both sides. Visual evoked potentials (VEP) showed prolongation of latencies. These results were compatible with PMD. Nuclear magnetic resonance imaging (MRI) demonstrated in the white matter of cerebrum and brainstem no high intensities on T1-weighted images and diffuse high intensities on T2-weighted images. Such absence of myelination including the brainstem was characteristic to the connatal type PMD. The diffuse disturbance of myelination appeared to correlate with the severity of clinical symptoms.     

A case of chorea-acanthocytosis with dilated cardiomyopathy and myopathy]

We report a patient of chorea-acanthocytosis (CA), presenting with dilated cardiomyopathy and myopathy. The patient, 40-year-old male, was seen in our clinic because of progressive gait disturbance. Neurologically, he had chorea, tic, dystonia, diminished tendon reflexes and mild muscular atrophy and weakness. Serum creatine kinase level was elevated to 5.514 IU/l, MRI study showed atrophy of the putamen and caudate nucleus. Peripheral nerve involvement was confirmed pathologically and electrophysiologically. Acanthocytosis was found after repeated blood examinations. Furthermore, he had dilated cardiomyopathy on echocardiogram and cardiac muscle biopsy, and his muscle biopsy taken from gastrocnemius indicated myopathic changes with fiber necrosis. From these clinical and laboratory data, he was suspected to have McLeod syndrome (McS). However, he had normal expression of Kell antigens, and direct sequence of XK gene from genomic DNA sample showed no mutations. Accordingly, he was diagnosed as having CA. As CA shares the similar clinical and laboratory features with McS except Kell antigens, the evaluation of Kell blood system is crucial for differential diagnosis. As seen in our patient, blood sampling should be repeated for identification of acanthocytosis, because the finding is not always clearly present.     

强迫症共病疾病焦虑障碍的临床访谈

为了提高广大精神心理科医务工作者的临床访谈及诊断技能,本文对一例较特殊的合并了两种强迫谱系障碍的患者进行了案例访谈报告。这是一位27岁的男性患者,执着于练习弹钢琴十几年,仪式化的行为与执着让患者不能正常工作,成为大家眼中的怪人。离职后逐渐开始关注排便问题,纠结于便秘、腹胀等感受问题,总认为自己患有肛肠疾病,开始反复检查就诊。在检查无明显异常的情况下,反复要求行手术治疗四次以解决肛肠问题,结果越治越难受。本案例患者被诊断为强迫症共病疾病焦虑障碍,需要采取生物-心理-社会的综合治疗。调整以往用药,加强运动,调整饮食结构。施行强迫症一线治疗方案,焦虑缓解后进行认知行为疗法(CBT)来改善自我认知,减轻心理压力。今后工作中放弃不切实际的想法,学习应对策略,合理安排工作和生活。     

A case of rigid spine syndrome with rimmed vacuole

A case of rigid spine syndrome associated with rimmed vacuoles in muscle biopsy is reported. A 36-year-old man was admitted to our hospital because of gait disturbance and limited mortality of the spine. His family was free from any neuromuscular disorders. He was born in normal pregnancy and delivery. His physical development was normal. At age 7, he was unable to run fast. At age 36, he had right hemiparesis and dysarthria. He was diagnosed as cerebral infarction of the left basal ganglia by brain CT. Neurological examination revealed moderate proximal dominant muscular atrophy and weakness. His spine was straight, showing loss of physiological cervical and lumbar lordosis. The neck flexion was limited but the extension was full. And he had contracture of bilateral ankle joint. Laboratory findings were all normal. The electrocardiogram showed negative T wave in V4, V5 and QT interval elongation. The echocardiogram showed diffuse decrease of ventricular wall motion. Respiratory function test revealed decrease of vital capacity. Arterial blood gases on room air showed that the PaO2 and PaCO2 were 70 mmHg and 49 mmHg, respectively. The findings of electromyogram were compatible with myopathic change. Biopsy specimen of the biceps brachii muscle showed marked variation in fiber size, type 1 fiber predominancy and atrophy, and type 2B fiber deficiency. Numerous rimmed vaculoes were found in the same muscle. Four cases of the rigid spine syndrome with rimmed vacuoles have been described. Among them, three patients died in young ages and two suffered from constrictive respiratory failure. In rigid spine syndrome with rimmed vacuole formation, the cardiac and respiratory problems must be taken account intensively.     

Severe tetanus in immunized patients with high anti-tetanus titers.

Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid. This is the first report of grade III tetanus with protective levels of antibody in the United States. The diagnosis of tetanus, nevertheless, should not be discarded solely on the basis of seemingly protective anti-tetanus titers.     

A patient with Parkinson's disease complicated by hypothyroidism who developed malignant syndrome after discontinuation of etizolam]

A 59-year-old man, who was diagnosed as having Parkinson's disease and depression seven years ago and was on oral antiparkinsonian agents, antianxiety agents, and antidepressants, developed a high fever, disturbed consciousness, and marked muscle rigidity after discontinuation of etizolam and amitriptyline. He was admitted to a nearby hospital. Hypothyroidism had been noted two months before admission. Marked muscle rigidity and increased serum CK were observed. Since discontinuation of benzodiazepine has been known to rarely trigger a neuroleptic malignant syndrome (NMS), he was diagnosed as having NMS. After receiving dantrolene and bromocriptine, these symptoms temporarily improved but he again developed consciousness disturbance, and convulsive seizures associated with an elevated serum CK. He was transferred to our hospital. On admission, the CK level was normal at 168 IU/l, while free T4 was 0.6 ng/dl (normal range, 0.9-2.3) and TSH was 108.7 mU/ml (normal range, 0.2-4.2) in serum, indicating the presence of primary hypothyroidism. As an increase in thyroid hormone dosage improved the thyroid function to normal level, his disturbed consciousness and muscle rigidity gradually improved. Convulsive seizure and recurrence of NMS in a short interval are unusual in neuroleptic malignant syndrome. In this patient, hypothyroidism may have contributed to the development of malignant syndrome through metabolic changes of the central dopaminergic system, and discontinuation of etizolam, a kind of benzodiazepine, may have triggered NMS, since there has not been reported that discontinuation of antidepressants including amitriptyline triggers NMS.     

Case of juvenile stroke caused by methylenetetrahydrofolate reductase deficiency

The patient had suffered from left hemiparesis at the age of thirteen months, and acute ischemic stroke of unknown etiology had been diagnosed at that time. His hemiparesis gradually disappeared and he was discharged two weeks after the onset without disability. At the age of 17 years, MRI following minor head trauma revealed cerebral infarctions located at the right corona radiata and basal ganglia. Laboratory findings showed hyperhomocysteinemia. Genetic study disclosed methylenetetrahydrofolate reductase deficiency (MTHFRD) (valine/valine type). MTHFRD is not detected by the routine infantile mass screening test for congenital amino acid metabolic disease, and should be considered in any patient with ischemic stroke at under two years of age.     

Cerebrotendinous xanthomatosis--a case of brain MRI abnormality and osteoporosis]

A 37-year-old male with cerebrotendinous xanthomatosis showed brain abnormal MRI findings and osteoporosis. His parents had no similar symptoms. He had mental retardation since childhood. Swelling of Achilles tendons was noticed at age 28, and gait disturbance appeared at age 34. Physical examination revealed bilateral cataracts and swelling of Achilles tendons. Neurologically, he showed mental retardation, cerebellar ataxia and spastic tetraparesis. Cerebrotendinous xanthomatosis was diagnosed by marked elevations of serum cholestanol level (24.3 micrograms/ml) and cholestanol/cholesterol ratio (1.81%) as well as characteristic clinical manifestations. On brain MRI study, T2-weighted sequence showed bilateral focal lesions with high intensity signal in the globus pallidus and cerebellar white matter adjacent to the dentate nucleus, and T1-weighted sequence showed low to iso-intensity signal in the same regions. These findings suggested demyelination rather than xanthoma or lipid infiltration. Radiological examination showed mild osteoporosis of lumbar bone. However, serum levels of vitamin D3 and calcitonin were within normal range, and renal function was normal. Osteoporosis in this patient possibly resulted from disuse bone atrophy for several years. The combination therapy of oral administration of chenodeoxycholic acid and HMG-CoA reductase inhibitor (pravastatin), and LDL apheresis slightly improved EEG abnormality and gait disturbance, but not brain MRI abnormality.     

Excessive daytime sleepiness after traumatic brain injury: association with periodic limb movements and REM behavior disorder: case report

A 52 year-old male patient, had complaint of "restless sleep". His wife informed that for the past ten years the patient had presented intense and aggressive body movements, and sometimes, violent dreams. The patient also complained of excessive daytime sleepiness. His relevant previous medical history included a traumatic brain injury at the age of 28 which left him in coma for two months. A video-polysomnography showed periodic leg movements and, during REM sleep, aggressive and agitated behaviour. The multiple sleep latency test revealed extremely short latencies. Initially, he was treated with levodopa-benzerazide, 100/25 mg, 2 hours before bedtime. After 10 weeks his overnight behaviour pattern improved and leg movements diminished. This case supports the hypothesis of an association between cranial trauma and alterations in the dopaminergic pathways represented by periodic leg movements during sleep and a sleep behaviour disorder and proposes the possibility of hypothalamic hypocretin involvement in its pathophysiology.