Diagnosis of peripheral neuropathy Lehmann, Helmar C; Wunderlich, Gilbert; Fink, Gereon R ...
Neurological research and practice,
07/2020, Letnik:
2, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Peripheral neuropathy represents a spectrum of diseases with different etiologies. The most common causes are diabetes, exposure to toxic substances including alcohol and chemotherapeutics, ...immune-mediated conditions, and gene mutations. A thorough workup including clinical history and examination, nerve conduction studies, and comprehensive laboratory tests is warranted to identify treatable causes.
The variability of symptoms allows distinguishing characteristic clinical phenotypes of peripheral neuropathy that should be recognized in order to stratify the diagnostic workup accordingly. Nerve conduction studies are essential to determine the phenotype (axonal versus demyelinating) and severity. Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy, represent additional clinical tests that can be useful in specific clinical scenarios.
We propose a flow chart based on five common basic clinical patterns of peripheral neuropathy. Based on these five clinical phenotypes, we suggest differential diagnostic pathways in order to establish the underlying cause.
The recognition of characteristic clinical phenotypes combined with nerve conduction studies allows pursuing subsequent diagnostic pathways that incorporate nerve conduction studies and additional diagnostic tests. This two-tiered approach promises higher yield and better cost-effectiveness in the diagnostic workup in patients with peripheral neuropathy.
Here we report on a patient with Parkinson's Disease and camptocormia due to Myofibrillar Myopathy Type 3. By leading the reader through the clinical reasoning process and highlighting the respective ...red flags we aim to increase the readers' awareness for the differential diagnosis of camptocormia.
In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of ...patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts.
An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented.
38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy.
This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.
Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We ...identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations. The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients. We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3596_3697insC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense-mediated decay. Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.
Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of motor neurons in the spinal cord, and comprises a broad clinical spectrum. With the advent of new ...therapies (e.g., Nusinersen) for patients of all ages and disease stages, sensitive clinical measures are needed to detect slight changes in muscle force even in immobilized, severely affected patients often unable to move limbs. As for these patients, well-established outcome scales set out to evaluate motor function do not work properly, we propose measurement of maximum bite force which is able to detect subtle changes of bulbar function. Requirements for this approach are mentioned, challenges are discussed, and first insights from a pilot study are presented. Finally, a study design is proposed to evaluate the measurement of maximum bite force during the follow up of SMA patients with and without a disease modifying therapy.
Small fiber neuropathy (SFN) is a challenging subtype of peripheral neuropathies. Once the diagnosis has been established, there is an uncertainty how SFN may progress, whether larger fibers will ...become involved over time, whether quality of life may be compromised, or whether repeated diagnostic workup in patients with unknown underlying cause may increase the yield of treatable causes of SFN.
We evaluated 16 patients with documented long-time course of idiopathic SFN.
Clinical and electrophysiological course remained stable in 75% of the patients, while 25% SFN-patients developed large fiber neuropathies.
Our data suggest that SFN represents a benign disease course in the majority of patients without severely limiting the quality of life.
Recently, a disease modifying therapy has become available for transthyretin amyloid cardiomyopathy (ATTR-CM). A validated monitoring concept of treatment is lacking, but a current expert consensus ...recommends three clinical domains (clinical, biomarker and ECG/imaging) assessed by several measurable features to define disease progression.
We retrospectively analyzed data of wild-type ATTR-CM patients initiating tafamidis therapy assessed within our local routine protocol at baseline and 6-months follow-up with respect to the frequency of values beyond the proposed thresholds defining disease progression. Additionally, associations of cardiac magnetic resonance (CMR) tomography with clinical domains were examined within a subgroup.
Sixty-two ATTR-CM patients were included (88.7% male, mean age 79 years). In total, 16.1% of patients had progress in the clinical and functional domain, 33.9% in the biomarker domain and 43.5% in the imaging/electrocardiography (ECG) domain, with the latter driven by deterioration of the diastolic dysfunction grade and global longitudinal strain. In total, 35.5% of patients showed progress in none, 35.5% in one, 29.0% in two and no patient in three domains, the latter indicating overall disease progression. A subgroup analysis of twenty-two patients with available baseline and follow-up CMR data revealed an increase in CMR-based extracellular volume by more than 5% in 18.2% of patients, with no significant correlation with progress in one of the clinical domains.
We provide first frequency estimates of the markers of disease progression according to a recent expert consensus statement, which might help refine the multiparametric monitoring concept in patients with ATTR-CM.
We investigated the role of the cerebellum in differential aspects of temporal control of rhythmic auditory motor synchronization using positron emission tomography (PET). Subjects tapped with their ...right index finger to metronome tones at a mean frequency of .8
Hz during 5 conditions: (1) an isochronous rhythm condition, (2) random changes in interval durations, and while the duration of rhythmic intervals was continuously time-modulated following a cosine-wave function at (3) 3%, (4) 7%, and (5) 20% of base interval. Anterior lobe cerebellar neuronal populations showed similar motor-associated activity across all conditions regardless of rhythmic time structure in vermal and hemispheric parts ipsilateral to the movements. Neuronal populations in bilateral anterior posterior lobe, especially in the simple lobule, increased their activity stepwise with each increase in tempo modulation from a steady beat. Neuronal populations in other parts of the posterior lobe showed an increase of activity only during the 20% condition, which involved conscious monitoring of rhythmic pattern synchronization, especially on the left side contralateral to the movements. Differential cerebellar activation patterns correspond to those in contralateral primary (primary sensorimotor), ipsilateral secondary (inferior parietal close to the intraparietal sulcus) and bilateral tertiary (dorsolateral prefrontal cortex) sensorimotor areas of the cerebral cortex, suggesting that distinct functional cortico-cerebellar circuits subserve differential aspects of rhythmic synchronization in regard to rhythmic motor control, conscious and subconscious response to temporal structure, and conscious monitoring of rhythmic pattern tracking.
PDF
