Distinct features between longitudinally extensive transverse myelitis presenting with and without anti-aquaporin 4 antibodies.

OBJECTIVES: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. METHODS: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. RESULTS: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-ß1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. CONCLUSION: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-ß treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.

Acute disseminated encephalomyelitis that meets modified McDonald criteria for dissemination in space is associated with a high probability of conversion to multiple sclerosis in Taiwanese patients.

BACKGROUND: Patients with acute disseminated encephalomyelitis (ADEM) may relapse and some may ultimately convert to multiple sclerosis (MS); however, no criteria that can predict MS conversion are available to date. Our aim was to describe the clinical and magnetic resonance imaging (MRI) features of patients with an initial ADEM attack and evaluate which MRI criteria can predict conversion to MS. METHODS: We retrospectively reviewed the records of 36 patients diagnosed with ADEM. We determined clinical signs/symptoms, examined the cerebrospinal fluid (CSF), and performed brain MRI scans and compared the findings between patients who did and did not convert to MS. RESULTS: Clinical signs/symptoms, and CSF analysis show no significant difference between the two groups. The rate of conversion to MS from ADEM in Taiwanese patients is low (11%) after a mean follow-up period of 28.36 months. Modified McDonald criteria were fulfilled in 19/36 patients: 21% (4/19) of those patients developed MS according to Poser criteria subsequently. Of the other patients (17/36) who did not fulfill these criteria, none converted to MS. (log rank test; P=0.027). CONCLUSIONS: It is difficult to predict from initial clinical presentations to address which patients with ADEM will convert to MS. Patients with ADEM whose brain MRI findings met the modified McDonald criteria may have clinically isolated syndrome because they have a significantly higher probability of conversion to MS. In contrast, patients whose brain MRI findings did not meeting these criteria may be considered as having classic ADEM because they have a lower probability of conversion to MS.

Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic hyperglycemic chorea-ballism patients.

BACKGROUND: Non-ketotic hyperglycemic chorea-ballism (NKHCB) had special reversible hyperintense on T1-weighted imaging (T1WI) lesion in comparsion to gray matter. However, the mechanism accounts for these lesions is still unclear. METHODS: Patients diagnosed with NKHCB were recruited from 2002 to 2004. The demographic, clinical, magnetic resonance imaging (MRI), and spectroscopy (MRS) features were recorded at acute and remission phase. RESULTS: In 18 patients with NKHCB, the blood sugar level at onset was significantly higher than that after being free from chorea-ballism (419.50 +/- 257.33 vs. 198.22 +/- 53.97 mg/dl, P = 0.001). The serum osmolality dropped from 318.33 +/- 15.21 mOsm/kg at onset to 292.50 +/- 7.85 mOsm/kg after recovery (P < 0.001). All patients displayed T1 hyperintense lesions at contralateral basal ganglia at acute phase. Eight patients receiving follow-up MRI at remission phase, all T1 hyperintense lesions at the basal ganglia regressed. The ratios between choline-containing compounds and creatine at acute and remission phases were significant higher in lesion than in normal side, respectively (acute phase: 1.12 +/- 0.23 vs. 0.72 +/- 0.28, P = 0.038; remission phase: 1.23 +/- 0.47 vs. 0.68 +/- 0.15, P = 0.013). The lactate peaks present at 1.3 ppm on the lesion side either in acute or in remission phase of most case. CONCLUSIONS: The clinical, MRI, and MRS findings suggest that the mechanisms responsible for NKHCB may be a reversible ischaemia insult potentiated by hyperglycemia.

Hypokalemic thyrotoxic periodic paralysis: clinical characteristics and predictors of recurrent paralytic attacks.

BACKGROUND AND PURPOSE: To study the clinical characteristics of hypokalemic thyrotoxic periodic paralysis (hoTPP) and identify the predictors of recurrent paralytic attacks before achieving the euthyroid status. METHODS: We retrospectively analyzed 45 hoTPP patients who were admitted during the 7-year study period. RESULTS: A tendency towards male predominance was observed among the 45 patients (91.1%, 41/45). The mean onset age was 32.9 +/- 10.0 years (range: 16-54 years). No significant differences were observed in the onset age between male and female patients. Precipitating factors included rest/sleep at night, hot weather, upper respiratory tract infections (URIs), and excessive physical activities. Atypical weakness was observed in nine (20%, 9/45) patients. One patient initially diagnosed with sporadic periodic paralysis eventually developed hoTPP. DISCUSSION: In provocative tests, hypokalemia was not a consistent finding during paralytic attacks. Before achieving the euthyroid status, the rate of recurrent attacks was as high as 62.2%, and peaked in the first 3 months after hoTPP was diagnosed. Patients with URIs exhibited a higher incidence of recurrent paralytic attacks than those without (odds ratio = 13.00; 95% confidence interval = 1.08-156.08; P = 0.04).

Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan.

BACKGROUND AND PURPOSE: This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case-control study. METHODS: Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. RESULTS: Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1-6.5, P = 0.02) was associated with female SDICH. CONCLUSIONS: This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan.

Contribution of clinical screening to carrier detection in a large Chinese family with Fabry disease due to a novel alpha-galactosidase A gene deletion.

Diagnosis of heterozygous Fabry patients is difficult because of its variable clinical manifestations and overlapping serum alpha-galactosidase A (AGA) activity between carriers and non-carriers. We tried to facilitate diagnosis of heterozygous Fabry patients by detailed clinical examination. We analyzed clinical presentations, biochemical, electrophysiological and genetic characteristics of 16 patients with Fabry disease in a large Chinese family. Male patients demonstrated significantly higher pain scores, poorer renal function, and higher frequency of hypohidrosis and corpora angiokeratomas than female patients. Interestingly, all the males and females had corneal verticilata by slit lamp examination. However, there was no association of serum AGA activity with renal function or pain symptom scores. The results indicated that detailed ocular and neurological examination might provide an alternative way of detecting heterozygous patients. We also report a novel large deletion spanning across the joint of Alu repetitive elements in introns 1 and 2 with resultant exon 2 deletion in a Chinese family with Fabry disease.

Isolated ocular motor nerve palsy in dural carotid-cavernous sinus fistula.

The incidence of dural carotid-cavernous sinus fistula (DCCF) presenting as isolated ocular motor nerve palsies without congestive ocular features is unknown. We reviewed the DCCF patients in our hospital during the last 10 years to elucidate the clinical and neuroradiological features of DCCF with isolated ocular motor nerve palsy. Eleven amongst the 33 DCCF patients presented isolated ocular motor nerve palsy. All the 11 patients underwent brain CT/CT angiography (CTA) and/or MRI/MR angiography (MRA), before the digital subtraction angiography (DSA). The compromised nerves were the oculomotor nerve in eight (72.7%), abducens nerve in two (18.2%) and trochlear nerve in one (9.1%). Brain CT and/or CTA were conducted in four patients but all unremarkable. MRI and/or MRA were performed in nine patients and six of them showed compatible findings of DCCF. The diagnoses of DCCFs were confirmed by DSA and all were posterior-draining type. The outcome was good, with a total recovery rate of 54.5% within 12 months. Thirty-three percent (11 of 33) of our DCCF patients presented with isolated ocular motor nerve palsy, which is not uncommon. MRI and MRA are of value in the initial evaluation, but DSA is necessary for the accurate diagnosis and treatment planning.

Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve.

The systemic administration of anti-nerve growth factor (NGF) antibodies can prevent local sensory hypersensitivity and block nociceptive fibers from sprouting into denervated adult rat skin. However, in the case of chronic constriction injury (CCI) in a rat, there is evidence that NGF reverses some effects of axotomy and alleviates thermal hyperalgesia. It is with this in mind that we investigated the influence of local anti-NGF and NGF on neuropathic pain and collateral sprouting caused by CCI. In our study, we looked at the effects to the ligated nerves after 30 consecutive days of local injections of anti-NGF and NGF. A high-dose of anti-NGF (1800 ng) was found to eradicate heat and cold hyperalgesia during postoperative days 16-28 and from days 8 to 34 after CCI, respectively. Our results show that a low-dose anti-NGF (18 ng) only mildly alleviates heat hyperalgesia but not cold hyperalgesia. There is evidence that a rebound phenomenon occurs for a short period of time after the anti-NGF injections cease. Results show that anti-NGF injections, whether in a high or low dose, significantly reduces the severity of autotomy or prevents the spread of collateral sprouting from the saphenous nerve into the sciatic innervation territory. In contrast, when a NGF (0.75 ng/g body weight) was applied to the ligated nerve immediately after the ligation, heat and cold hyperalgesia were eradicated during postoperative days 4-68 and from days 4 to 28, respectively. The results show that the effect of anti-NGF is delayed at the onset, is short in duration, and is dependent on the dosage. However, anti-NGF but not NGF blocked collateral sprouting and decreased the severity of autotomy, suggesting that anti-NGF may be a better potential alternative analgesic for the treatment of neuropathic pain in humans. The different initiation times to abolish thermal hyperalgesia by anti-NGF (delayed onset) and NGF (early onset) suggests that alterations in neurotrophic factors contribute to the development of behavioral hyperalgesia via a complex mechanism in CCI rats.

Local application of anti-NGF blocks the collateral sprouting in rats following chronic constriction injury of the sciatic nerve.

Systemic administration of anti-nerve growth factor (NGF) antibodies can block nociceptive fiber sprouting into denervated adult rat skin. However, the effect of local application of anti-NGF on collateral sprouting in rats caused by chronic constriction injury (CCI) has not been well studied. We investigated the influence of local anti-NGF on collateral sprouting caused by CCI of the rat's sciatic nerve. Using a dye-labeled plasma extravasation technique, we can easily evaluate the extent of collateral sprouting by the clearly defined blue coloration area. Our results showed that local application of anti-NGF either in a high or low dose significantly prevented the spread of collateral sprouting from the saphenous nerve into the sciatic innervation territory. In contrast, distilled water did not show a significant block of the saphenous nerve collateral sprouting. Our study suggests that collateral sprouting is dependent on the local availability of NGF by the nearby intact cutaneous nerve fibers.

Hirayama disease: MR diagnosis.

We report the MR findings in two cases of Hirayama disease, a kind of cervical myelopathy related to flexion movements of the neck. In flexion MR studies, we can see the striking and pathognomonic picture of anterior shifting of posterior dura at the lower cervical spinal canal. In nonflexion studies, we find that asymmetric cord atrophy, especially at the lower cervical cord, though subtle, is highly suggestive of Hirayama disease. When it is seen, a flexion MR study is warranted to prove this diagnosis.

A morphological study of experimental mononeuropathy in the rat: early ischemic changes.

This paper describes early morphological changes following the placement of four loose ligatures round the rat sciatic nerve, a method used to produce altered pain-related behaviour. The ligatures were tied so as not to constrict the nerve, but there was compression of some epineurial blood vessels. This mild lesion caused behavioural changes and nerve fiber abnormalities within 8.5 h. The distribution of nerve fiber changes was patchy, and initially due to stagnant ischemia, with necrosis of Schwann cells and evidence of axonal stasis. By 48 h, endoneurial oedema increased leading to a compressive lesion and eventually to severe nerve fiber degeneration.

Concurrent trigeminal, abducens, and facial nerve palsies presenting as false localizing signs: case report.

Multiple cranial nerve dysfunction presenting as false localizing signs is rare. We report a 20-year-old woman who had concurrent trigeminal sensory disturbance, abducens, and peripheral facial nerve palsies in association with a contralateral acoustic neuroma. After surgery, the trigeminal nerve disturbance and the abducens nerve palsy completely recovered, but the peripheral facial nerve palsy persisted. The nature of tumor, the presence of brain stem distortion, the anatomic variation of posterior fossa, and the relationships of cranial nerves and nearby blood vessels, which are factors influencing the occurrence of false localizing, are briefly discussed.

Transient global amnesia and amaurosis fugax in a patient with common carotid artery occlusion--a case report.

The etiology of transient global amnesia (TGA) is debatable. The hypothesis of a thromboembolic cause of TGA has been questioned by recent case control studies. Occlusion of the common carotid artery (CCA) is rare. Although amaurosis fugax (AF) is a hallmark of ipsilateral internal carotid artery disease, its occurrence in CCA occlusion is less known. Association of these three conditions in a patient may imply pathophysiologic significance. Here, the authors report a 76-year-old man who suffered from a spell of TGA and then several attacks of AF of the right eye. Progressive occlusion of the right CCA was documented by repeat carotid duplex scans and was finally confirmed by cerebral angiography. In this patient, the occurrence of CCA occlusion and AF implicates a vascular etiology for the event of TGA. A noninvasive carotid ultrasonographic screen may, therefore, be worthwhile for patients with TGA.

Extent of collateral sprouting of intact nerve fibers in rats depends on the local availability of nerve growth factor.

We investigated the influence of local administration of anti-nerve growth factor (NGF) serum on collateral nerve fiber sprouting caused by chronic constriction injury (CCI) of the sciatic nerve in rats. CCI was induced in adult Sprague-Dawley rats (six per group) by constriction of the sciatic nerve of the right hind limb. Control rats received no further manipulation. In four other groups, rabbit preimmune (control) serum or low (18 ng) or high (1800 ng) doses of anti-NGF serum were injected into the operated or unoperated hind limb each day for 1 month. We used an Evans dye-labeled plasma extravasation technique to visualize the extent of collateral sprouting. Local injection of anti-NGF serum at both high and low doses, but not control serum, significantly reduced the spread of collateral sprouting from the saphenous nerve into the sciatic nerve innervation territory. High-dose anti-NGF serum did not block collateral sprouting when injected into the contralateral (unoperated) hind limb, indicating that the inhibition of sprouting was not caused by a systemic effect. In conclusion, local administration of anti-NGF serum can block sprouting of collateral fibers after nerve injury. Our findings suggest that collateral sprouting is dependent on the local availability of NGF to nearby intact cutaneous nerve fibers.

Fabry's disease: report of a case.

Fabry's disease is a rare hereditary disorder of glycosphingolipid metabolism. Its clinical features have not been adequately described in Taiwan. This paper reports on a 32-year-old man who had painful acroparesthesia, disseminated skin angiokeratomas, whorled corneal opacity, mitral valve prolapse and renal insufficiency. There was also involvement of the central motor pathways and the autonomic nervous system. A sural nerve biopsy showed loss of small myelinated and unmyelinated fibers. A reduced serum activity of alpha-galactosidase A and a large amount of urinary globotriaosylceramide confirmed the diagnosis of Fabry's disease.

Juvenile-onset of Dejerine-Sottas disease in a Taiwanese woman.

Dejerine-Sottas disease is an uncommon hereditary neuropathy which has not been reported in Taiwan. We describe a 57-year-old woman who had slowly progressive weakness in her four limbs since adolescence. None of her close relatives had the disease and no consanguinity was noted. Neurologic examination showed severe weakness and vibratory sensation loss in the four limbs. The tendon reflexes were generally absent. Electrophysiologic studies suggested a systemic myelinopathic process. Light and electron microscopy of the sural nerve biopsy specimens revealed many onion-bulb shapes formed by the Schwann cell processes or basement membranes without any evidence of myelin sheaths around the axons, which are characteristic features of Dejerine-Sottas disease.

Idiopathic hypereosinophilic syndrome with eosinophilic myositis, peripheral neuropathy and central nervous system involvement.

Idiopathic hypereosinophilic syndrome (HES) is a rare disorder marked by a sustained overproduction of eosinophils and a predilection for damage to multiple organ systems. Its neurologic involvement ranges from the central to the peripheral nervous system, and can be associated with eosinophilic myositis. We report a 68-year-old woman who had eosinophilia, eosinophilic dermatitis and eosinophilic pneumonia. She also suffered from numbness and weakness of the lower limbs. Because of long-lasting (> 6 mo) eosinophilia (> 1.5 x 10(9)/L) in the peripheral blood and the fact that no other underlying causes of eosinophilia and neurologic involvement could be identified, a diagnosis of idiopathic hypereosinophilic syndrome was made. The muscle biopsy showed infiltration of inflammatory cells, including a few eosinophils (Liu's stain). Magnetic resonance images, motor evoked potentials, somatosensory evoked potentials and nerve conduction velocities also showed abnormalities in the central and peripheral nervous systems. The pathogenesis and treatments of HES are discussed in this report.

Vocal cord paralysis as an initial sign of multiple system atrophy in the central nervous system.

Multiple system atrophy (MSA) of the central nervous system has been recognized as a rare cause of stridor secondary to vocal cord paralysis. This respiratory problem usually occurs in the later stages of the disease. We report the case of a 53-year-old man who presented with bilateral vocal cord paralysis accompanied by stridor and sleep apnea, which were relieved by a tracheostomy. Two years after the onset of stridor, he developed extrapyramidal and cerebellar signs combined with severe autonomic failure. Magnetic resonance imaging of the brain revealed atrophy of the brainstem and cerebellum. This clinical picture is consistent with the diagnosis of MSA. Vocal cord paralysis preceding any other neurologic and autonomic manifestations has been infrequently described. This case should remind clinicians that MSA should be considered in the differential diagnosis of vocal cord palsy of undetermined origin.

gamma-sarcoglycan deficiency muscular dystrophy in two adults.

All dystrophin-associated proteins contain sarcoglycan complex. Different forms of muscular dystrophy are caused by defective expression of different proteins of this structure. gamma-Sarcoglycan deficiency muscular dystrophy, so-called severe childhood autosomal recessive muscular dystrophy (SCARMD), is a rare disease that has not been previously reported in Taiwan. This paper describes two Taiwanese adults with this disease: a 26-year-old man with calf pseudohypertrophy who had weakness in both legs for 1 year; and a 43-year-old woman who had progressive weakness in all four limbs, with the initial symptom of gait disturbance at the age of 32 years. Analysis of muscle biopsy specimens, which showed total deficiency of gamma-sarcoglycan protein on immunostaining, confirmed the diagnosis of SCARMD in both cases. However, the clinical manifestations in these two patients, including lower proximal limb weakness initially developing in adulthood with a slow progressive course, are different from previously reported cases of SCARMD. The literature on this disease is reviewed and possible mechanisms of these distinct clinical presentations are discussed.