Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis

Objective

The characteristic pathological muscular findings of polymyositis (PM) and dermatomyositis (DM) have been shown to reflect their different pathogeneses. Here, we characterized the muscle biopsy findings of PM and DM patients with or without malignancy.

Methods

We evaluated the muscle biopsy findings of 215 consecutive PM and DM patients admitted to our hospital between 1970 and 2009. Pathology of the lesion biopsy sections was classified into 3 types: endomysial infiltration-type, perivascular infiltration-type, and rare-infiltrative-type.

Results

There was no difference between the muscle pathology of PM patients with and without malignancy. However, the incidence of rare-infiltrative type muscle pathology in DM patients with malignancy was significantly higher than in those without such tumors (p = 0.0345).

Conclusion

The incidence of rare-infiltrative type muscle pathology may be a predictive marker of DM with malignancy.     

Evaluation of brain biopsy in the diagnosis of severe neurologic disease of unknown etiology

Objective

To determine the value of non-stereotactic brain biopsies in patients with severe neurologic disease of unknown etiology and indeterminate brain imaging.

Methods

We reviewed 42 consecutive patients who underwent non-stereotactic brain biopsy at a single institution for evaluation of severe neurologic disease of unknown etiology. All patients had indeterminate or normal imaging results. Seventy-nine percent had been symptomatic for less than a year. Exclusion criteria were immunocompromise or a preoperative diagnosis of intracranial neoplasm. Diagnostic yield and surgical complication rate were calculated. We performed exploratory univariate analysis aimed at identifying clinical features possibly predictive of diagnostic biopsies.

Results

A histologic diagnosis was achieved in 12 of 42 biopsies (29%). Three patients experienced minor transient complications from the procedure (7%). There were no permanent deficits or deaths. Treatment was altered based on biopsy result in five patients (12%). A more precise prognosis was obtained in eight patients (19%). In total, 11 different patients (26%) benefited from biopsy. Exploratory univariate analysis showed a possible inverse relationship between age and the likelihood of a diagnostic biopsy (OR = 0.929; 95% CI = 0.864–0.998).

Conclusions

Our data suggest that the value of non-stereotactic brain biopsy is sufficiently high and the morbidity sufficiently low to justify its use in carefully selected patients with severe neurologic disease that remains undiagnosed despite thorough less invasive evaluation.     

Diagnostic utility of skin biopsy in dystrophinopathies

Aims

Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy.

Methods

Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies.

Results

Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%).

Conclusion

Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy.     

Quantitative studies of lower motor neuron degeneration in amyotrophic lateral sclerosis: Evidence for exponential decay of motor unit numbers and greatest rate of loss at the site of onset

Objective

To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS.

Methods

In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution.

Results

The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset.

Conclusions

The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of disease.

Significance

This shows that the Bayesian MUNE method is useful in following the course and exploring the clinical features of ALS.     

Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours

Background

There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection.

Materials and methods

Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department. Among these patients we identified 51 patients, who underwent magnetic resonance (MR) based stereotactic biopsy and subsequent open resection within 30 days. Mortality and morbidity data as well as final histopathological diagnoses of both procedures were compared with regard to tumour grade and tumour cell type. Patients with discrepancies between the histological diagnosis obtained by biopsy and open resection were classified into three subgroups (same cell type but different grading; same grading but different cell type and different grading as well as different cell type).

Results

The mean number of tissue samples taken by stereotactic serial biopsy from each patient was 12 (range 7–21). Minor morbidity was 6% and major morbidity was 14% after open surgery compared to no morbidity after stereotactic biopsy. Mortality was 2% after stereotactic biopsy (one patient died after stereotactic biopsy as a result of a fatal bleeding) compared to 0% in the resection group. Silent bleeding rate without any clinical symptoms was 8% in the biopsy group. A complete correlation of histopathological findings between the biopsy group and the resection group was achieved in 76% and was increased to 90% by analyzing clinical and neuroradiological information. In patients with recurrence the correlation was higher (94%) than for patients with primary brain lesions (67%). The discrepancies between the open resection group and biopsy group were analysed.

Conclusion

Stereotactic MR guided serial biopsy is a minimal invasive procedure with low morbidity and high diagnostic accuracy for diagnosis and grading of brain tumours. Diagnostic accuracy of stereotactic biopsy can be enhanced further by careful interpretation of neuroradiological and clinical information.     

Electrical stimulation site influences the spatial distribution of motor units recruited in tibialis anterior

Objective

To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk.

Methods

Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation.

Results

During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M_max; M_5%max), 50% M_max (M_50%max) and 95% M_max (M_95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M_5%max, M_50%max or M_95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions.

Conclusions

Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude.

Significance

These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data.     

The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1(G93A) mice

Objective

To assess the relationship between Bayesian MUNE and histological motor neuron counts in wild-type mice and in an animal model of ALS.

Methods

We performed Bayesian MUNE paired with histological counts of motor neurons in the lumbar spinal cord of wild-type mice and transgenic SOD1^G93A mice that show progressive weakness over time. We evaluated the number of acetylcholine endplates that were innervated by a presynaptic nerve.

Results

In wild-type mice, the motor unit number in the gastrocnemius muscle estimated by Bayesian MUNE was approximately half the number of motor neurons in the region of the spinal cord that contains the cell bodies of the motor neurons supplying the hindlimb crural flexor muscles. In SOD1^G93A mice, motor neuron numbers declined over time. This was associated with motor endplate denervation at the end-stage of disease.

Conclusion

The number of motor neurons in the spinal cord of wild-type mice is proportional to the number of motor units estimated by Bayesian MUNE. In SOD1^G93A mice, there is a lower number of estimated motor units compared to the number of spinal cord motor neurons at the end-stage of disease, and this is associated with disruption of the neuromuscular junction.

Significance

Our finding that the Bayesian MUNE method gives estimates of motor unit numbers that are proportional to the numbers of motor neurons in the spinal cord supports the clinical use of Bayesian MUNE in monitoring motor unit loss in ALS patients.     

Comprehensive evaluation of EMG and biopsy findings supported by computer simulations – A preliminary study

Objective

The aim was to compare muscle fiber diameters obtained from standard muscle biopsy and from computer simulations based on recorded motor unit potentials (MUPs).

Stereotactic brain biopsy: Single center retrospective analysis of complications

Objective

Stereotactic biopsy is a widely used surgical technique for the histological diagnosis of intracranial lesions. Potential risks of this procedure, such as hemorrhage, seizure, and infection have been established, and different risk factors have been characterized. However, these risks have been addressed by only few studies conducted in Asian countries.

Materials and methods

The study group is comprised of 299 consecutive stereotactic biopsy procedures by 11 neurosurgeons between 2004 and 2007. The pre-operative medical conditions, methods of biopsy and postoperative complications were analyzed.

Result

The overall diagnostic yield was 90.64%. Complications were observed in 7.36% of the cases, with symptomatic hemorrhages occurring in 4.35% of the cases, and the overall mortality rate in this study population was 1.34%. Patients with liver cirrhosis were at a higher risk of hemorrhage. Other clinical, radiological, or histological variables were not associated with an increased risk of complications.

Conclusion

Stereotactic brain biopsy is a safe and reliable way to obtain a histological diagnosis. Based on our recent clinical experiences, the data suggests that more attention should be paid to liver cirrhotic patients, since the chance on hemorrhage is significantly larger.     

Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders

Objective

Motor unit recruitment order and firing rate was investigated in healthy subjects, and in small numbers of patients 50 years ago. We aimed to investigate firing rate in different disorders, testing the same target muscle with normal strength, to evaluate possible application in diagnosing upper motor neuron (UMN) lesion.

Methods

We studied motor unit firing in the tibialis anterior muscle in six groups of subjects; normal subjects (n = 45), patients with amyotrophic lateral sclerosis (ALS) (n = 36), primary lateral sclerosis (PLS) (n = 21), progressive muscular atrophy (PMA) (n = 14), various upper motor neurone lesions (n = 16) and polyneuropathy (n = 42). In all these subjects the tibialis anterior muscle was of normal strength. Motor units were recruited during slight contraction in order to study 2–5 motor units at each recording site, using a standard concentric needle electrode, so that 20–22 motor units were recorded in each muscle. We analysed the coefficient of variation (CV) for amplitude, area, duration and firing rate in these motor units, and the correlation between motor unit potential size and recruitment order.

Results

The mean MU firing rate in this task was similar in each group. No recruitment order was disclosed within the limits of the study task. The CV of firing rate was decreased in UMN and PLS groups. ALS patients with marked spasticity showed a lower CV of motor unit firing rate. The CV of amplitude, area and duration was similar between groups.

Conclusions

These results in tibialis anterior indicate that physiological modulation of lower motor neuron (LMN) firing rate is decreased in patients with lower limb spasticity. The variability of MU discharges tends to be greater in diseases affecting the LMN.

Significance

These results suggest that, notwithstanding the simplicity of the task we have used, the physiological variability of motor unit firing may be a useful variable in assessing UMN involvement in motor system disorders.     

Phrenic nerve studies predict survival in amyotrophic lateral sclerosis

Objective

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease associated with short survival due to respiratory failure. We aimed to test the predictive value of the phrenic nerve motor response for survival, in a large population of ALS patients.

Methods

We included 254 ALS patients followed in our tertiary centre from 1997 to 2006, in whom phrenic nerve stimulation was performed according to the study inclusion and exclusion criteria. ALS was spinal onset in 175 and bulbar onset in 79 patients. The following features were recorded at entry: gender, age at presentation, onset region, diagnostic delay, forced vital capacity (FVC), ALS functional rating scale (ALS-FRS) including the respiratory subscore of the reviewed ALS-FRS and mean amplitude of motor responses by phrenic nerve stimulation (PhrenAmpl).

Results

Survival analysis was evaluated by Kaplan–Meier log-rank test and multivariate Cox proportional hazards. Independent factors negatively affecting survival were bulbar onset, short diagnostic delay, FVC and small PhrenAmpl for the total population. Small PhrenAmpl and short diagnostic delay were also independent factors for both spinal and bulbar-onset patients; age at onset and FVC were also independent predictors in bulbar-onset patients.

Conclusion

Phrenic nerve stimulation is a non-volitional test that can be performed quickly in most patients; it is a powerful predictor of survival in ALS.

Significance

Phrenic nerve stimulation should be considered as an additional test for respiratory assessment in ALS.     

Glycerol rhizotomy via a retrosigmoid approach as an alternative treatment for trigeminal neuralgia

Objectives

Trigeminal neuralgia is a sensory nerve disorder characterized by lancinating pain and treated most commonly with carbamazepine, rhizotomy treatment, or open surgical management with microvascular decompression. We describe a novel technique to complement surgical treatment for trigeminal neuralgia via direct injection of the trigeminal nerve with glycerin in the cisternal portion of the nerve.

Patients and methods

We performed a retrospective analysis of patients who received standard microvascular decompression and injection of glycerin to the inferior third of the cisternal portion of the nerve anterior to the root entry zone with lack of a compressive vessel on MRI as the primary indication. Fourteen patients were identified and demographic information, post-operative course and complications were recorded.

Results

There were eleven females and three males with an average age at time of surgery of 54.8 years. 100% of patients reported that their trigeminal pain was significantly improved following surgical intervention. Four out of fourteen patients reported a 50–80% decrease from the pre-surgery baseline pain at one month and three month follow up. One patient developed a CSF leak, and no surgical site infections or motor deficits were observed.

Conclusion

Intra-operative glycerin rhizotomy in conjunction with microvascular decompression can be used to safely treat patients suffering from trigeminal neuralgia.     

Deficient muscle activation in patients with Complex Regional Pain Syndrome and abnormal hand postures: An electromyographic evaluation

Objective

Motor abnormalities in Complex Regional Pain Syndrome (CRPS) are common and often characterized by a restricted active range of motion (AROM) and an increased resistance to passive movements, whereby the affected body part preferably adopts an abnormal posture. The objective of the present study was to obtain a better understanding of the factors that are associated with these abnormal postures and limitations of the AROM, and to investigate whether these motor impairments reflect dystonia.

Methods

We evaluated characteristics of surface EMG of the flexor carpi radialis and extensor carpi radialis muscles during active maintenance of various flexion–extension postures of the wrist of the affected and unaffected side in 15 chronic CRPS patients, and in 15 healthy controls.

Results

Deviant joint postures in chronic CRPS – at least in those patients with some range of active movement – were not characterized by sustained muscle contractions, and limitations of the AROM were not attributable to excessive co-contraction. Rather, the agonistic muscle and its antagonist were activated in normal proportions, albeit over a limited range.

Conclusions

The AROM limitations and abnormal postures that are often observed in chronic CRPS patients are not associated with excessive muscle activity and hence do not exhibit the characteristics typical of dystonia.

Significance

We hypothesize that structural alterations in skeletal muscle tissue and pain-induced adaptations of motor function may contribute to the observed motor impairments. Our findings may have important clinical implications, since commonly prescribed treatments are aimed at reducing excessive muscle contraction.     

DYSF mutation analysis in a group of Chinese patients with dysferlinopathy

Objective

Dysferlinopathies belong to heterogeneous group of autosomal recessive muscular disorders caused by mutations in the gene encoding dysferlin. The classifications of the dysferlinopathies mainly include limb-girdle muscular dystrophy 2B (LGMD2B) with predominantly proximal weakness, Miyoshi myopathy (MM) with calf muscle weakness and atrophy, and distal myopathy with anterior tibial onset (DMAT) with tibialis muscle atrophy. We describe the genetic character of dysferlinopathies in a group of Chinese patients.

Methods

DYSF mutations screening were done after muscle biopsy and immunohistochemical staining.

Results

Eight patients showed an absence or drastic decrease of dysferlin expression in biopsied muscle. We identified 6 different mutations, including one nonsense mutation, two insertion mutation, two deletion mutations and one splice site mutation. Five of them were novel mutations.

Conclusion

We described 8 Chinese patients with dysferlinopathy (four had a distal phenotype of MM; one had a phenotype of DMAT and three presented with LGMD2B). It is the first report of genetic confirmed DMAT in China. Mutations c.3112C>T and c.1045dup, may be recurrent mutations in China.     

Atypical motor unit potentials in Emery–Dreifuss muscular dystrophy (EDMD)

Objective

The aim of the study was to analyse electromyographic changes in Emery–Dreifuss muscular dystrophy (EDMD) that are atypical for myopathy. Our special interest was focused on high amplitude polyphasic motor unit potentials (MUPs), also termed irregular MUPs.

Endoscopy in the management of intra-ventricular lesions: Preliminary experience in the Middle East

Objectives

The study is aimed at evaluating neuroendoscopic procedures in the management of various intra-cranial intra-ventricular lesions.

Methods

We retrospectively review 24 consecutive patients harboring various intra-ventricular lesions with or without associated hydrocephalus, operated and managed by the authors between December 2002 and December 2007. Depending on the preoperative imaging and working diagnosis, endoscopic biopsy or endoscopic resection/debulking, along with concomitant treatment of hydrocephalus via third ventriculostomy or fenestration of the septum pellucidum and ventriculo-peritoneal shunting, were done.

Results

The single endoscopic procedure was successful in most of the patients (22/24), where the goals of surgery in attaining a diagnostic biopsy or resection, and simultaneous treatment of hydrocephalus, were attained helping guide further therapy. The endoscopic procedure was the only procedure needed in most of the patients.

Conclusions

The endoscopic procedures carried a high success rate in the management of intra-ventricular lesions, and were especially valuable in patients harboring chemo and/or radiosensitive deep seated tumors.     

The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic,nerve ultrasound and histological study

Objective

Nerve ultrasound (US) data on myelin protein zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology.

Correlation between compound muscle action potential amplitude and duration in axonal and demyelinating polyneuropathy

Objective

To get a better understanding of pathophysiology in polyneuropathies (PNPs) by correlating compound muscle action potential (CMAP) amplitude with duration.

Methods

A total of 145 motor nerve conduction studies (MNCS) in 53 axonal and 132 MNCS in 45 demyelinating PNPs were analyzed. Peroneal and tibial MNCS were done by surface stimulation while for median and ulnar nerves near nerve or surface stimulations were used. CMAP amplitude and duration were compared in axonal and demyelination PNPs. Relationships between amplitude and duration of distally and proximally evoked CMAP were examined using regression analysis.

Results

CMAP amplitude was lower and duration was increased in all examined nerves in demyelinating PNPs than in axonal PNPs. In demyelinating PNPs, an inverse linear correlation between amplitude and duration was seen in distally and proximally evoked CMAP in all examined nerves. In axonal PNPs, there was no correlation in any of the nerves neither in distally nor in proximally evoked CMAP.

Conclusions

Distal CMAP duration and the relationship between CMAP amplitude and duration show supplementary electrodiagnostic potential in demyelinating PNPs.

Significance

More knowledge about the relation between amplitude and duration in axonal lesions and demyelination may help to reveal the pathophysiology in PNPs. Significant correlation between amplitude and duration in demyelination may suggest that the severe decrease in amplitude in demyelinating PNPs is probably due to the increase in duration secondary to temporal dispersion.     

Spectroscopy-supported frame-based image-guided stereotactic biopsy of parenchymal brain lesions: Comparative evaluation of diagnostic yield and diagnostic accuracy

Objective

Comparative evaluation of diagnostic efficacy of stereotactic brain biopsy performed with and without additional use of spectroscopic imaging (¹H-MRS) for target selection was done.

Methods

From 2002 to 2006, 30 patients with parenchymal brain lesions underwent ¹H-MRS-supported frame-based stereotactic biopsy, whereas in 39 others MRI-guided technique was used. Comparison of diagnostic yield of the procedure in these two groups was performed. Additionally, the diagnostic accuracy was evaluated in 37 lesions, which were surgically resected within 1 month thereafter.

Results

Stereotactic biopsy permitted establishment of a definitive histopathological diagnosis in 57 cases and diagnosis of low-grade glioma without specific tumor typing in 8 cases. In 4 cases tissue sampling was non-diagnostic. In 5 out of 8 cases with incomplete diagnosis and in all non-diagnostic cases target selection was performed without the use of ¹H-MRS (P = 0.2073). The diagnostic yields of ¹H-MRS-supported and MRI-guided procedures were 100% and 90%, respectively (P = 0.1268). Comparison of the histopathological diagnoses after stereotactic biopsy and surgical resection revealed complete diagnostic agreement in 13 cases, minor disagreement in 14 cases, and major disagreement in 10 cases. Among these last 10 cases, initial undergrading of non-enhancing WHO grade III gliomas was the most common (7 cases). The diagnostic accuracy of ¹H-MRS-supported and MRI-guided procedures was 67% and 79%, respectively (P = 0.4756).

Conclusion

While in the present study the diagnostic yield of ¹H-MRS-supported frame-based stereotactic brain biopsy was 100%, its statistically significant diagnostic advantages over MRI-guided technique were not proved. Optimal selection of the spectroscopic target for tissue sampling remains unclear.     

Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury

Objective

Incomplete spinal cord injury (iSCI) disrupts motor control and limits the ability to coordinate muscles for overground walking. Inappropriate muscle activity has been proposed as a source of clinically observed walking deficits after iSCI. We hypothesized that persons with iSCI exhibit lower locomotor complexity compared to able-body (AB) controls as reflected by fewer motor modules, as well as, altered module composition and activation.

Methods

Eight persons with iSCI and eight age-matched AB controls walked overground at prescribed cadences. Electromyograms of fourteen single leg muscles were recorded. Non-negative matrix factorization was used to identify the composition and activation of motor modules, which represent groups of consistently co-activated muscles that accounted for 90% of variability in muscle activity.

Results

Motor module number, composition, and activation were significantly altered in persons with iSCI as compared to AB controls during overground walking at self-selected cadences. However, there was no significant difference in module number between persons with iSCI and AB controls when cadence and assistive device were matched.

Conclusions

Muscle coordination during overground walking is impaired after chronic iSCI.

Significance

Our results are indicative of neuromuscular constraints on muscle coordination after iSCI. Altered muscle coordination contributes to person-specific gait deficits during overground walking.