Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study.

BACKGROUND: Bullous pemphigoid (BP) has been associated with neurological and psychiatric diseases; however, large-scale population-based study of different comorbid diseases in patients with BP is quite limited. OBJECTIVES: We sought to analyse the prevalence of neurological, psychiatric, autoimmune and inflammatory skin diseases prior to the diagnosis of BP and their associations with BP among patients with BP from a nationwide database in Taiwan. METHODS: A total of 3485 patients with BP and 17,425 matching controls were identified from the National Health Insurance Database in Taiwan from 1997 to 2008. Conditional logistic regression analyses for a nested case-control study were performed to examine the prevalence of comorbidities prior to the diagnosis of BP between these two groups. RESULTS: Overall, our results showed that stroke [odds ratio (OR) 3·30; 95% confidence interval (95% CI) 3·03-3·60], dementia (OR 4·81; 95% CI 4·26-5·42), Parkinson disease (OR 3·49; 95% CI 3·05-3·98), epilepsy (OR 3·97; 95% CI 3·28-4·81), schizophrenia (OR 2·56; 95% CI 1·52-4·30) and psoriasis (OR 2·02; 95% CI 1·54-2·66) were significantly associated with BP. Among them, the association with schizophrenia and psoriasis was predominant in female and male patients, respectively, with BP. It remains for all these comorbid diseases to be independently associated with BP by multivariate analysis. CONCLUSIONS: Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.

Effect of sacral-root stimulation on the motor cortex in patients with idiopathic overactive bladder syndrome.

AIMS OF THE STUDY: It is presumed that idiopathic overactive bladder syndrome (OBS) is due to visceral hypersensitivity. Sacral-root stimulation can restore the bladder function, but its mechanism remains uncertain. It is well-known that long-term peripheral stimulation can induce brain plasticity. Hence, we investigated whether brain reorganization occurred along with clinical improvement after sacral-root stimulation. MATERIAL AND METHODS: Because toe flexion is the index for monitoring wire placement, we used the flexor hallucis brevis (FHB) as the target muscle. Transcranial magnetic stimulation (TMS) was applied to study motor cortex excitability and the brain mapping of the muscle. RESULTS: Six patients with idiopathic OBS were included in the study. All demonstrated clinical improvement after sacral-root stimulation. Motor cortex excitability and the area of representation for the flexor hallucis brevis muscle increased for at least 30 min after sacral-root stimulation had terminated. CONCLUSION: Our results showed that cerebral activities changed after sacral-root stimulation. The improvement in urinary urgency and urgency perception was probably due in part to brain reorganization.

MR findings of decerebrate rigidity with preservation of consciousness.

We describe a case of decerebrate rigidity, with preservation of consciousness, caused by a discrete pontine tegmentum lesion identified on MR imaging. Lesions within a certain brain stem region are responsible for decerebrate rigidity in animal studies, but there has been a lack of MR imaging evidence in humans. This report also implies that a discrete lesion was responsible for the decerebrate rigidity, while consciousness was preserved.

Functional recovery of chronic complete idiopathic transverse myelitis after administration of neurotrophic factors.

STUDY DESIGN: Case report. OBJECTIVE: To evaluate the functional recovery of chronic complete idiopathic transverse myelitis (ITM) after administration of acidic fibroblast growth factor (aFGF). METHODS: A 28-year-old woman presented with a 4-year history of spastic paralysis, sensory level at T10, urinary retention and constipation due to ITM. In all, 20 microg aFGF bolus injection was applied via intradural lumbar puncture, which was repeated every 5 months for 15 months. RESULTS: At 3 weeks after first injection, the patient experienced vague sensation at approximately T12-L1 dermatomes. At 2 months after the second injection, muscle activities and gait pattern were recorded in bilateral gluteus and hip abductors as she ambulated with long leg brace and axillary crutches. Increased walking speeds, reduced pelvic tilting and reduced compensatory trunk rotation during the swing phase were also demonstrated as compared to the initial gait analysis. At 18 months after injection, motor evoked potentials were obtained in hip abductors of both legs. CONCLUSIONS: aFGF may increase the efficacy of spinal reactivation/regeneration and is a potential remedy for chronic transverse myelitis.

Valproate-induced encephalopathy.

A 50-year-old woman taking carbamazepine (CBZ) 1200 mg daily for her partial epilepsy developed acute confusion after valproate (VPA) add-on treatment for 10 days. The administration of VPA started from 1000 mg daily and, 3 days later, increased to 1500 mg daily. Beside a mildly elevated serum ammonia level (81 microg/dL), her electroencephalogram showed diffuse background slowing intermixed with 2-2.5 Hz of high-amplitude slow waves, which indicated a diffuse encephalopathy. The serum levels of VPA and CBZ were 49.1 mg/L and 8.6 mg/L, both being non-toxic. The liver functions appeared normal. She recovered rapidly after discontinuation of VPA. In this patient, a safe previous administration of VPA did not preclude the occurrence of encephalopathy. A relatively large initial VPA dosage could possibly be the culprit.

Single-pulse transcranial magnetic stimulation reset the rhythm of essential tremor but not heart beat.

BACKGROUND: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is generated by heart itself but can be modulated by brain. Using the technique of transcranial magnetic stimulation (TMS) and resetting index, we studied if single-pulse TMS could reset the cardiac rhythm and help differentiate oscillator of neurogenic or non-neurogenic origin. METHODS: In addition to the study of 4 patients with essential tremor, cardiac rhythm was studied in 6 normal subjects. The magnetic intensity was initiated from motor threshold of hand muscle, and then with an increment of 10% up to the maximal output of magnetic stimulator. We used the resetting index (RI) to quantify the influence of the TMS. RESULTS: The resetting phenomenon was observed in essential tremor (RI = 0.92) but not in cardiac rhythm (RI = 0.02). CONCLUSIONS: Single-pulse TMS is able to reset the rhythm of essential tremor but not heart beat. The pacing mechanism is different between essential tremor and heart beat. The cardiac rhythm is regulated and modulated chiefly by heart itself. Essential tremor should not share the same mechanism with heart beat.

Brain dysfunction explored by long latency reflex: a study of adrenomyeloneuropathy.

OBJECTIVES: We can assess brain function by measuring the cortical relay time (CRT) of long latency reflex (LLR) of hand muscle. We would study if measurement of CRT of LLR can explore the brain involvement of adrenomyeloneuropathy (AMN). METHODS: Two AMN patients were included in the study. Both of them had spastic gait and mild sensory deficits but normal mental function. The LLRs were provoked at the first dorsal interosseous muscle by electrical stimulation of the middle finger. We measured the latency of LLR and its CRT. RESULTS: Delayed LLR and prolonged CRT were noted in AMN patients, even though the magnetic resonance imaging of brain did not show any significant abnormalities. CONCLUSIONS: Measuring CRT of LLR reveals brain involvement of AMN patients, and it is an adjunct in the assessment of brain function though without specific anatomic diagnosis.

Bilateral neurotrophic keratopathy complicating Vidian neurectomy.

PURPOSE: To present a case of bilateral neurotrophic keratopathy with miosis after bilateral Vidian neurectomy for vasomotor rhinitis. METHODS: Observational case report. RESULTS: A 68 year-old man presented with irritation and blurred vision in both eyes 2 weeks after bilateral Vidian neurectomy. Slit-lamp examination revealed a large epithelial defect, typical of neurotrophic keratopathy, in the inferior two-thirds of cornea in both eyes. Corneal sensitivity test with a Cochet-Bonnet anesthesiometer and electrical study of the blink reflex indicated bilateral trigeminal dysfunction. Both pupils were miotic, and tests with hydroxyamphetamine 1% and epinephrine 0.1% showed postganglionic sympathetic nerve damage. The corneal epithelial defects healed after 2 months of treatment with systemic prednisolone, vitamin B(12) and tarsorrhaphy. CONCLUSION: Neurotrophic keratopathy associated with dry eye syndrome may be a serious complication of Vidian neurectomy.

Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism.

A genetic analysis identified 2 patients, approximately one-tenth of our patients with familial parkinsonism, who had expanded trinucleotide repeats in SCA2 genes. The reduction of 18F-dopa distribution in both the putamen and caudate nuclei confirmed that the nigrostriatal dopaminergic system was involved in parkinsonian patients with SCA2 mutation.

Problem-based, small-group tutorial learning in clinical neurology for second-year medical students.

BACKGROUND: Problem-based learning (PBL) in small-group tutorials has been a trend in medical education. Chinese students are known to be reserved and passive; thus, they may not be adaptable to PBL. Neuroanatomy, important to clinical neurology, is difficult to learn. We incorporated clinical neurology with PBL, complementary to the traditional neuroanatomy curriculum, to evaluate the feasibility of PBL for Chinese students in Taiwan. METHODS: Forty-two second-year medical students and seven tutors participated in the clinical neurology PBL small-group tutorials. Twelve case reports were discussed weekly beginning in February, 1999. Each case was designed to meet the progressive curriculum of the neuroanatomy course. The tutors evaluated the students by the degree of their preparation, participation, key-point comprehension and interaction. All tutors and students filled out questionnaires at the end of each session. RESULTS: The majority of the students and tutors agreed that the case materials were clearly written. Ninety percent of the students agreed that the case materials matched the traditional content of neuroanatomy. Eighty-five percent of students and 71% of tutors were satisfied and found the class rewarding. Ninety-one percent of students and 74% of tutors were in favor of PBL being continued. CONCLUSIONS: This preliminary PBL, small-group tutorial learning in clinical neurology showed satisfactory results and was, indeed, complementary to a traditional neuroanatomy course. The students, as early as during the second year of their medical school education, were able to learn through the PBL. More integration of basic and clinical sciences by PBL may be considered in future curricula designs.

Modulation of symptomatic palatal tremor by magnetic stimulation of the motor cortex.

OBJECTIVES: Magnetic stimulation of the motor cortex can be used to determine the involvement of the cortex in rhythmic movement disorders. Symptomatic palatal tremor (SPT) is thought to come from a pacemaker that is relatively resistant to internal and external stimulation. In this study, we investigated the effect of magnetic stimulation of motor cortex on SPT. METHODS: Five male patients, aged 67-79 years, with SPT after brain stem infarction or hemorrhage, all had a synchronous mouth angle twitch with the palatal movement. Electromyographic activity was recorded with a monopolar needle electrode from orbicularis oris. In experiment 1, transcranial magnetic stimulation (TMS) was delivered at 200% motor threshold (MT) to reset SPT. In experiment 2, the effect of TMS intensities was studied at 80-240% MT in two SPT patients. To determine the influence of the TMS, we used the resetting index (RI). RESULTS: TMS reset the tremor in all 5 SPT patients at 200% MT with RIs of 0.86-0.96. The latency of the tremor reappearance after TMS was longer than the pre-stimulus tremor interval, and the intervals between the subsequent tremor bursts were also prolonged. The degree of tremor resetting was closely correlated with the magnetic stimulus intensity and the latency of the tremor reappearance after TMS. CONCLUSIONS: Stimulation of the motor cortex may modulate the generator of SPT.

Age effect of type I collagen on morphogenesis of Mardin-Darby canine kidney cells.

BACKGROUND: Mardin-Darby canine kidney (MDCK) cells cultured in hydrated collagen gels develop simple epithelial cysts or branching tubules, depending on the presence of hepatocyte growth factor (HGF). Constituents of extracellular matrix can modulate the morphogenesis of MDCK cells. Collagen is one of the few well-defined structural entities that display gross structural changes with aging. This study was conducted to delineate the effects of age-induced changes of collagen on the morphogenesis of MDCK cells cultured in collagen gel. METHODS: We employed Y224 and MDCK clone II 3B5 cells to study cystogenesis and branching tubulogenesis, respectively. Cells were cultured in three-dimensional collagen gels prepared from 1-, 4-, 8-, and 16-month-old rat tail tendons, and their capacity to develop cysts or branching tubules was assessed. We also analyzed the compositions and physical structures of collagen of various ages. RESULTS: Y224 cells developed generally larger spherical cysts in collagen gels prepared from rats that were more than four months old. The ratio of apoptosis of cells cultured in one-month-old collagen gel was markedly higher than in the gel of older ages. The results were consistent with the observations that collagen gel overlay-induced apoptosis of Y224 cells in one-month-old collagen was higher than that in older collagen. On the other hand, 3B5 cells exhibited a remarkable scattering morphology when cultured in one- or four-month-old collagen gel with HGF. In contrast, 3B5 cells exhibited more intercellular adhesion and were organized into branching tubule structures only in the collagen gel that was more than eight months old. The differences in morphogenesis could be explained by the observations that collagen of younger ages exerted markedly higher HGF-triggered migration capability than collagen of older ages. CONCLUSIONS: Age-related alterations in collagen influence epithelial cell morphogenesis via regulation of cell apoptosis, proliferation, and/or motility.

Detecting alveolar epithelial injury following volatile anesthetics by (99m)Tc DTPA radioaerosol inhalation lung scan.

BACKGROUND: Many volatile anesthetics have long been thought to affect alveolar epithelial permeability. OBJECTIVE: The purpose of this study was to examine the acute effects of volatile anesthetics on the permeability of the alveolocapillary barrier to (99m)Tc DTPA. METHODS: Twenty-seven patients (24 females, 3 males, age 29-73 years) undergoing operation were enrolled in this study and grouped according to the type of anesthesia received. Group 1 patients were administered 1% halothane. Group 2 patients were given 1.5% isoflurane. Intravenous anesthesia without volatile anesthetics were used for group 3 patients. Before and after anesthesia, (99m)Tc DTPA radioaerosol inhalation lung scans were performed to detect alveolar epithelial injury due to volatile anesthetics. The negative slope of the regression line was designated as the (99m)Tc DTPA pulmonary clearance rate and was expressed in terms of percentage decrease in radioactivity per minute. RESULTS: In group 1, the (99m)Tc DTPA clearance rates were 1.26 +/- 0.34 and 1.29 +/- 0.38 before and after anesthesia, respectively. The difference was not significant (p > 0.05). In group 2, the rates were 0.76 +/- 0.20 and 1.10 +/- 0. 37, before and after anesthesia, respectively. The difference was significant (p < 0.05). In group 3, the clearance rates were 1.07 +/- 0.38 and 1.21 +/- 0.48, before and after anesthesia, respectively. The difference was not significant. CONCLUSIONS: Following isoflurane administration, the more rapid pulmonary clearance of (99m)Tc DTPA indicates that isoflurane increases the permeability of the alveolo-capillary barrier.

Botulism: heart rate variation, sympathetic skin responses, and plasma norepinephrine.

BACKGROUND: Botulism may involve the autonomic nervous system. METHODS: We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine. RESULTS: Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole. Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 +/- 1.2% vs. 20.9 +/- 2.0%, p = 0.0018) and during deep breathing (4.3 +/- 2.3% vs. 29.7 +/- 2.6%, p = 0.0018). The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 +/- 10.1 pg/ml vs. 257.5 +/- 65.8 pg/ml, p = 0.0018; standing 40.3 +/- 13.1 pg/ml vs. 498.5 +/- 85.6 pg/ml, p = 0.0018). The heart rate variation and sympathetic skin response was greatly improved 6 months after onset. CONCLUSIONS: Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

Effect of stimulation of an upper limb on motor evoked potentials in lower limb muscles to transcranial magnetic stimulation in normal subjects and patients with thalamic infarction.

The effects of conditioning stimulation of an upper limb on motor evoked potentials (MEPs) of relaxed muscles in both lower limbs were studied in 7 normal subjects and two patients with left thalamic infarction. A possible mechanism for the Jendrassik maneuver (JM) is that induced proprioceptive input ascends supraspinally to facilitate the descending volleys. In order to mimic the JM with a more controlled influence, we used an electrical conditioning (C) stimulation (4 times sensory threshold) delivered to the left index finger preceding the transcranial (T) magnetic stimulation at C-T intervals of 0-200 ms. The MEP facilitation of bilateral tibialis anterior (TA) and gastrocnemius medialis (GC) was within C-T 70-110 ms. The peak facilitation was at C-T 80 ms for ipsilateral TA (309%) and GC (405%) and at C-T 90 ms for contralateral TA (207%) and GC (283%). In the two thalamic infarction patients with right-sided sensory loss, the facilitation did not occur when the conditioning stimulation was delivered to the affected index finger. Therefore, it is likely that the peripheral volley must be transmitted supraspinally to facilitate MEPs of the lower limbs. This method for studying sensory facilitation is more quantitative and reproducible than the JM and technically better than other previously described methods for somatosensory conditioning.

Evidence for decreased salivary function in patients with reflux esophagitis.

It has been speculated that impaired salivary flow contributes to abnormal acid clearance of the esophagus in gastroesophageal reflux and results in reflux esophagitis (RE). To test this hypothesis, salivary functions were measured by quantitative salivary scintigraphies in patients with RE and in age- and sex-matched controls for comparison. Nineteen patients with RE and 36 healthy volunteers were enrolled in the study. After an intravenous injection of 5 mCi Tc-99m pertechnetate, sequential images of 1 min/frame were acquired for 30 min. The 1- and 15-min uptake ratios (UR) of the tracer in the four major salivary glands over the backgrounds were calculated. Saliva excretion was stimulated by 1 tablet of 200 mg ascorbic acid given orally 15 min after injection of the tracer, then the maximal excretion ratios (ER) of the four major salivary glands were calculated for the sialagogue stimulation. RE patients had lower values of 1st and 15th min UR and maximal ER than controls in the 4 major salivary glands. Poor salivary functions which represented a decrease in both UR and ER for patients with RE have been confirmed by quantitative salivary scintigraphy in this study.

Use of botulinum toxin A in the treatment of hemifacial spasm and blepharospasm.

BACKGROUND: Hemifacial spasm and blepharospasm are both dystonic disorders. They may seriously affect individuals' lifestyle and social activities. In 1990, the Food and Drug Administration of the USA approved botulinum toxin A as a therapeutic agent in the treatment of hemifacial spasm and blepharospasm. We present a therapeutic review of botulinum toxin A in 80 patients in Taiwan. METHODS: Fifty-eight patients with hemifacial spasm and 22 with blepharospasm. Botulinum toxin A was prepared and injected into the facial and eyelid muscles. Patients were monitored every two weeks and classified into four groups (excellent, moderate, mild and no improvement) according to the clinical improvement scale. Complications were also recorded. RESULTS: A total of 86.2% of hemifacial spasm patients and 81.8% of blepharospasm patients had excellent improvement on the spasm intensity scale, while 6.8% of hemifacial spasm and 9.0% of blepharospasm patients had moderate improvement. The complication rate was low and included transient mild facial weakness (5%), ptosis (3.8%), eyelid swelling and/or ecchymosis (3.8%), nausea/vomiting (2.5%) and transient severe facial weakness (1.3%). CONCLUSION: Botulinum toxin A is an excellent therapeutic agent to improve spasm intensity and has a low complication rate.

A trial study of leukocyte labeling with stabilized Tc-99m D,L-HMPAO by methylene blue and sodium phosphate buffer.

UNLABELLED: We attempted to label leukocytes with stabilized Tc-99m D,L-HMPAO by methylene blue and sodium phosphate buffer (S-HMPAO). METHODS: The results were compared with unstabilized Tc-99m D,L-HMPAO (U-HMPAO). U-HMPAO was obtained by reconstituting a commercial vial of D,L-HMPAO. Stabilization of the kit was performed by the addition of methylene blue. The leukocytes were labeled using a modified published method. The test samples of S-HMPAO and U-HMPAO were prepared immediately, and stood for 0.5, 1, 2, 4, and 6 h, respectively, at room temperature before analysis. RESULTS: In comparison with U-HMPAO: (1) the radiochemical purity of S-HMPAO was higher; (2) the labeling efficiencies of S-HMPAO labeled leukocytes were higher and consistent; (3) the viability of S-HMPAO labeled leukocytes was as high as the viability of U-HMPAO labeled leukocytes at any time; and (4) the percentages of disintegrated from S-HMPAO labeled leukocytes in plasma were lower. CONCLUSION: S-HMPAO is more stable than U-HMPAO and can provide higher leukocyte labeling efficiency. S-HMPAO, therefore, has the potential to replace U-HMPAO as a leukocyte-labeling agent.