Sien-Tsong Chen

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.

Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: A hospital-based case-control study

We investigated the relationship between the most common 4977‐bp deleted mitochondrial DNA (mtDNA) mutations and the occurrence of sporadic amyotrophic lateral sclerosis (ALS). Primer‐shift and quantitative polymerase chain reaction (PCR) were used to determine the 4977‐bp deleted mtDNA in the muscle specimens from 36 patients with sporadic ALS and 69 age‐matched controls with other neuromuscular disorders. We found that the 4977‐bp deleted mtDNA mutations were significantly higher in the ALS patients than controls in both frequency (50.0% vs. 8.7%, P < 0.01) and amount (0.35 ± 0.53% vs. 0.085 ± 0.35%, P < 0.05). Subjects with, rather than without, deleted mtDNA were at a significantly higher risk for having ALS after adjustment for age and sex. Moreover, male subjects had a higher risk than female subjects of having sporadic ALS. This study suggested that 4977‐bp deleted mtDNA is significantly associated with the occurrence of sporadic ALS. Muscle Nerve 28: 737–743, 2003

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

Background and purpose:u2002 To study the clinical characteristics of hypokalemic thyrotoxic periodic paralysis (hoTPP) and identify the predictors of recurrent paralytic attacks before achieving the euthyroid status.

Current perception threshold testing in Fabry's disease.

We investigated 16 patients with Fabrys disease (eight hemizygous men and eight heterozygous women) in one family. We used constant current perception threshold (CPT) testing, which evaluated three major sensory nerve fiber populations, to assess subjective complaints of pain and paresthesias. We also examined clinical and biochemical features and compared the values of CPTs and nerve conduction studies (NCS) in detecting the sensory neuropathy. Our results showed that CPT testing at low frequencies (5 and 250 Hz) was significantly more sensitive than at a higher frequency (2 kHz) and NCS in detecting sensory neuropathy in patients with Fabrys disease. However, there was no correlation between CPT testing and clinical symptom scores, duration of disease, creatinine clearance (Ccr) values or α‐galactosidase A (AGA) activities in either hemizygous or heterozygous patients. Hemizygous patients clinically demonstrated more severe symptom scores, poorer renal function, and higher prevalence of hypohidrosis and corpora angiokeratomas than did heterozygous patients, which indicates that detailed clinical examinations can differentiate the clinical status of hemizygous men from heterozygous women. There were no associations between the biochemical levels of serum AGA activity and renal function (Ccr values) or the symptom scores (grading of acroparesthesia), indicating that biochemical parameters do not predict clinical severity.

Recurrent hypertensive intracerebral hemorrhage

Hypertensive intracerebral hemorrhage has been considered as a one‐time event with rare recurrence. This observation is quite different from our experience in Taiwan. We, therefore, conducted a systematic review of our series of consecutive patients with recurrent bleeding. During a 2‐year period, we encountered 47 patients with recurrent hypertensive intracerebral hemorrhage from a total of 892 consecutive patients with hypertensive hemorrhage (5.3%). There were 25 men and 22 women with a mean age of 59 ± 10 (range: 36–78) years at the onset of the first hemorrhage and 62 ± 9 (range: 39–80) years at the second hemorrhage. The median interval between 2 hemorrhages was 2 years and 4 months (range: 1 month to 8.5 years). All except one recurrent hemorrhages occurred at a site different from the previous one. Of the 38 patients admitted to our hospital for both hemorrhages only 5 were regularly treated with antihypertensive therapy. The outcome for the recurrent bleeding was grave: 26% died and 51% became totally dependent or vegetative. Recurrent hypertensive hemorrhage is not as rare as previously thought; it comprises 5.3% of our patients with hypertensive intracerebral hemorrhage. The recurrent hemorrhage, however, rarely occurs at the same location as the previous one. Uncontrolled hypertension appears to be an important risk factor for the recurrence. Control of blood pressure after the first bleeding should be attempted to prevent recurrent hemorrhage.

Are there ethnic differences in impulsive/compulsive behaviors in Parkinson’s disease?

Background and purpose:u2002 Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson’s disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS).

Territorial and extra-territorial distribution of Fos protein in the lumbar spinal dorsal horn neurons in rats with chronic constriction nerve injuries.

This study aimed to examine the relationship between temporal and spatial expression patterns of Fos protein in the spinal dorsal horn neurons and thermal hyperalgesia behaviors in rats with chronic constriction injury (CCI) to the sciatic nerve. Our results demonstrated that Fos protein expression in the spinal dorsal horn neurons at L5 segment ipsilateral and contralateral to CCI of the sciatic nerve was significantly greater than in sham rats from days 10 to 30 postoperatively (PO 10d to 30d), and was concentrated on the injury (ipsilateral) side. Unlike the short-lived expression after tissue inflammation, laminae I to VI (especially laminae III/IV) displayed a persistent greater number of Fos-like immunoreactive (Fos-LI) neurons for at least 30 days after CCI of the sciatic nerve. After the increase in laminae III/IV, Fos-LI neurons tended to gradually increase in laminae I/II and V/VI at L5 segment from PO 2d to 30d, which were correlated with the heat hyperalgesia (48 degrees C) behaviors measured by paw withdrawal latency in CCI rats but not in sham rats. Interestingly, a persistent increase of Fos-LI neurons in laminae I to VI at L5 segment of the ipsilateral and contralateral sides and at the L1 segment that was out of the normal central terminations of the sciatic nerve suggested the probable presence of territorial and extra-territorial central sensitization or inadequate central nervous system (CNS) adaptive mechanisms. These findings may partly explain why abnormal pain sensations are sometimes distributed in a pattern that does not coincide with the territories of nerves or with the posterior roots of the peripheral nerve after injury.

Concomitant spinal cord and vertebral body infarction is highly associated with aortic pathology: a clinical and magnetic resonance imaging study

The purpose of this article is to investigate the relationship between clinical features and imaging characteristics of spinal cord infarction (SCI). Twenty patients (11 women/9 men) were diagnosed at the Chang Gung Memorial Hospital between March 1993 and March 2007. Data of clinical features, possible causes and imaging findings were collected and analyzed retrospectively. Their average age was 56.6xa0±xa015.5xa0years. Possible causes of SCI were found in 16 patients (80%), including 8 (40%) who had a high risk of atherosclerosis, 5 (25%) who had aortic diseases, and 3 (15%) who had adjacent spinal diseases; the other 4 (20%) were cryptogenic. Seven patients had concomitant SCI and vertebral body infarctions, and four of them had aortic diseases. Most of the vertebral body infarctions were seen in the thoracolumbar regions (pxa0=xa00.008, χ2 test) and were adjacent to their cord lesions. Twelve patients (60%) had poor outcomes (mortality, unable to walk, or able to walk with two aids). Younger patients (≤55xa0year-old) with long cord lesions (greater than or equal to three vertebral segments) had poorer outcomes than older patients with short cord lesions. Vertebral abnormalities are not uncommon, but easily overlooked in SCI. Furthermore, concomitant SCI and vertebral body infarctions were usually located at the thoracolumbar regions, and highly associated with patients with aortic diseases (pxa0=xa00.03, χ2 test). An understanding of the spinal cord and vertebral vascular supply greatly benefits in early diagnosis, etiological illumination, and prognostic prediction of SCI.

Parkinsonism in a patient with antiphospholipid syndrome — Case report and literature review

Antiphospholipid syndrome (APS) is identified as the presence of antiphospholipid antibodies (aPLs) in patients with vascular thrombosis and/or pregnancy morbidity (including fetal death, premature birth and habitual abortion). Neurological manifestations in patients with APS are common, whereas movement disorders are rarely seen. We report an extremely rare case of APS presented with parkinsonism and review the literature to address the clinical profile and possible pathophysiologic mechanism of this disorder.

Spontaneous intrapetrous internal carotid artery dissection: A case report and literature review

Although hemodynamic change has been identified as the main mechanism of infarcts in intracranial internal carotid artery dissection, no report has utilized computed tomography perfusion study to evaluate the cerebral flow change in such cases. This report presents a rare case of intrapetrous internal carotid artery dissection with watershed infarction. Additionally, a literature review addresses the clinical profiles and related neuroimaging findings of such patients.