Parsonage-Turner Syndrome and Hereditary Brachial Plexus Neuropathy.

Parsonage-Turner syndrome and hereditary brachial plexus neuropathy (HBPN) present with indistinguishable attacks of rapid-onset severe shoulder and arm pain, disabling weakness, and early muscle atrophy. Their combined incidence ranges from 3 to 100 in 100,000 persons per year. Dominant mutations of SEPT9 are the only known mutations responsible for HBPN. Parsonage and Turner termed the disorder "brachial neuralgic amyotrophy," highlighting neuropathic pain and muscle atrophy. Modern electrodiagnostic and imaging testing assists the diagnosis in distinction from mimicking disorders. Shoulder and upper limb nerves outside the brachial plexus are commonly affected including the phrenic nerve where diaphragm ultrasound improves diagnosis. Magnetic resonance imaging can show multifocal T2 nerve and muscle hyperintensities with nerve hourglass swellings and constrictions identifiable also by ultrasound. An inflammatory immune component is suggested by nerve biopsies and associated infectious, immunization, trauma, surgery, and childbirth triggers. High-dose pulsed steroids assist initial pain control; however, weakness and subsequent pain are not clearly responsive to steroids and instead benefit from time, physical therapy, and non-narcotic pain medications. Recurrent attacks in HBPN are common and prophylactic steroids or intravenous immunoglobulin may reduce surgical- or childbirth-induced attacks. Rehabilitation focusing on restoring functional scapular mechanics, energy conservation, contracture prevention, and pain management are critical. Lifetime residual pain and weakness are rare with most making dramatic functional recovery. Tendon transfers can be used when recovery does not occur after 18 months. Early neurolysis and nerve grafts are controversial. This review provides an update including new diagnostic tools, new associations, and new interventions crossing multiple medical disciplines.

[MR neurography reveals fascicular constriction of the median nerve in a patient with neuralgic amyotrophy].

Diagnosing neuralgic amyotrophy can be challenging in clinical practice. Here, we report the case of a 37-years old Japanese woman who suddenly developed neuropathic pain in the right upper limb after influenza vaccination. The pain, especially at night, was severe and unrelenting, which disturbed her sleep. However, X-ray and MRI did not reveal any fractures or muscle injuries, and brain MRI did not reveal any abnormalities. During neurological consultation, she was in a posture of flexion at the elbow and adduction at the shoulder. Manual muscle testing suggested weakness of the flexor pollicis longus, pronator quadratus, flexor carpi radialis (FCR), and pronator teres (PT), while the flexor digitorum profundus was intact. Medical history and neurological examination suggested neuralgic amyotrophy, particularly anterior interosseous nerve syndrome (AINS) with PT/FCR involvement. Innervation patterns on muscle MRI were compatible with the clinical findings. Conservative treatment with pain medication and oral corticosteroids relieved the pain to minimum discomfort, whereas weakness remained for approximately 3 months. For surgical exploration, lesions above the elbow and fascicles of the median nerve before branching to the PT/FCR were indicated on neurological examinations; thus, we performed high-resolution imaging to detect possible pathognomonic fascicular constrictions. While fascicular constrictions were not evident on ultrasonography, MR neurography indicated fascicular constriction proximal to the elbow joint line, of which the medial topographical regions of the median nerve were abnormally enlarged and showed marked hyperintensity on short-tau inversion recovery. In patients with AINS, when spontaneous regeneration cannot be expected, timely surgical exploration should be considered for a good outcome. In our case, MR neurography was a useful modality for assessing fascicular constrictions when the imaging protocols were appropriately optimized based on clinical assessment.

[Diagnostics and treatment of hourglass-like nerve constrictions and torsions in neuralgic amyotrophy]. / Diagnostik und Therapie sanduhrförmiger Nervenstrikturen und -torsionen bei neuralgischer Amyotrophie.

Neuralgic amyotrophy is a disease of the peripheral nervous system characterized by severe neuropathic pain followed by peripheral paralysis. A distinction is made between a hereditary and an idiopathic form, which is assumed to have an autoimmunological origin. Conservative medicinal treatment mainly consists of nonsteroidal anti-inflammatory drugs (NSAID), opioids and glucocorticoids; however, despite treatment, symptoms in the form of pain or paralysis persist in over 50% of cases. Inflammation can lead to strictures and torsions of peripheral nerves, which can be visualized by imaging using nerve sonography or magnetic resonance (MR) neurography and confirmed intraoperatively during surgical exploration. Based on the currently available data, patients with strictures and torsions of peripheral nerves can benefit from neurosurgical treatment.

The role of ultrasonography in diagnosis of neuralgic amyotrophy.

OBJECTIVE: To investigate the value of high frequency ultrasound in diagnosis of neuralgic amyotrophy. MATERIALS AND METHODS: From January 2010 to December 2020, the ultrasonographic images of 117 patients with neuralgic amyotrophy diagnosed by the Department of Neurology and hand & foot surgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University were retrospectively analyzed. The ultrasonographic features were summarized. RESULTS: High frequency ultrasound could clearly show the degree of the affected nerves: No ultrasonic findings were found in 12 cases (10%). The affected nerves were thickening and hypoechogenicity with loss of normal fascicular definition in 28 cases (24%). The affected nerves showed hourglass-like changes, including constriction and torsion in 77 cases (66%). In addition, ultrasound can determine the extent of the lesion, and microvascular imaging can display small blood flow signal within the nerve. There was a significant statistical difference between the diameter of the thickened nerve fascicle and the diameter of the nerve fascicle at the corresponding site of the contralateral normal limb. CONCLUSIONS: High frequency ultrasound is a valuable imaging method for diagnosis of neuralgic amyotrophy.

Neuralgic amyotrophy detected by magnetic resonance neurography: subclinical, bilateral, and multifocal brachial plexus involvement.

INTRODUCTION: Neuralgic amyotrophy (NA) is a painful non-traumatic peripheral nervous system condition affecting the brachial plexus. Signal abnormalities in nerves and muscles have been detected in these patients using magnetic resonance neurography (MRN). METHODS: Electronic medical records and MRN images obtained in a 3 T scanner, in 14 adult patients diagnosed with NA at our Neurological institution (Neuromuscular Disorders Section), between December 2015 and December 2019 were retrospectively reviewed. The study was first approved by our Institutional Ethics Committee. RESULTS: Subclinical, multifocal, and bilateral nerve signal anomalies were recorded in the brachial plexus of these patients. We identified four different types of nerve constriction without entrapment, which we categorized as follows: incomplete focal (type I), complete focal or hourglass (type II), multifocal or string of pearls (type III) and segmental (type IV). CONCLUSIONS: Given that MRN is an accurate diagnostic tool to detect nerve damage, we believe abnormal findings could improve early detection of NA patients.

Neuralgic amyotrophy triggered by cytomegalovirus: to be aware of this clinical diagnosis.

Neuralgic amyotrophy (NA) is a multifocal inflammatory neuropathy. Although the exact etiopathogenesis of the latter is unknown, the literature reports frequent associations with immunological events such as different infectious diseases. Our case reveals a rarely described etiology of NA. NA is mainly a clinical diagnosis. The etiology shown in our case study is interesting for the scientific community, because CMV is an ubiquitous disease. NA is frequently under-recognized and misdiagnosed. This is particularly common in the early phase of the disease, when neurologic signs have not yet developed.

Tomodensitometric bone anatomy of the intervertebral foramen of the lower cervical spine: measurements and comparison of foraminal volume in healthy individuals and patients suffering from cervicobrachial neuralgia due to foraminal stenosis.

PURPOSE: Degenerative foraminal stenosis of the cervical spine can lead to cervicobrachial neuralgias. Computed tomography (CT)-scan assists in the diagnosis and evaluation of foraminal stenosis. The main objective of this study is to determine the bony dimensions of the cervical intervertebral foramen and to identify which foraminal measurements are most affected by degenerative disorders of the cervical spine. These data could be applied to the surgical treatment of this pathology, helping surgeons to focus on specific areas during decompression procedures. METHODS: A descriptive study was conducted between two groups: an asymptomatic one (young people with no evidence of degenerative cervical spine disorders) and a symptomatic one (experiencing cervicobrachial neuralgia due to degenerative foraminal stenosis). Using CT scans, we determined a method allowing measurements of the following foraminal dimensions: foraminal height (FH), foraminal length (FL), foraminal width in its lateral part ((UWPP, MWPP and IWPP (respectively Upper, Medial and Inferior Width of Pedicle Part)) and medial part (UWMP, MWMP and IWMP (respectively Upper, Medial and Inferior Width of Medial Part)), and disk height (DH). Foraminal volume (FV) was calculated considering the above data. Mean volumes were measured in the asymptomatic group and compared to the values obtained in the symptomatic group. RESULTS: Both groups were made up of 10 patients, and a total of 50 intervertebral discs (100 intervertebral foramina) were analyzed in each group. Comparison of C4C5, C5C6 and C6C7 levels between both groups showed several significant decreases in foraminal dimensions (p < 0.05) as well as in foraminal volume (p < 0.001) in the symptomatic group. The most affected dimensions were UWPP, MWPP, UWMP, MWMP and FV. The most stenotic foraminal areas were the top of the uncus and the posterior edge of the lower plate of the overlying vertebra. CONCLUSION: Using a new protocol for measuring foraminal volume, the present study refines the current knowledge of the normal and pathological anatomy of the lower cervical spine and allows us to understand the foraminal sites most affected by degenerative stenosis. Those findings can be applied to foraminal stenosis surgeries. According to our results, decompression of the foramen in regard of both uncus osteophytic spurs and inferior plate of the overlying vertebra might be an important step for spinal nerves release.

Parsonage-Turner syndrome and cytomegalovirus disease.

Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome (PTS), is a distinct idiopathic immune-mediated neuritis of the brachial plexus, characterized by sudden attacks of severe neuropathic pain usually in the shoulder and/or arm, followed by progressive neurologic deficits, including weakness, atrophy, and occasionally sensory abnormalities. Pathogenesis is assumed to be multifactorial, and several observations support the hypothesis of an immune-triggering event preceding PTS, most frequently infections. A literature review reveals a variety of clinical presentations and courses. Various microorganisms preceding PTS have been documented. The authors report a case of PTS related to cytomegalovirus infection with a review of the relevant literature. Special emphasis is placed on the most important infectious agents considered in the etiological list of PTS.

Neuralgic amyotrophy: a paradigm shift in diagnosis and treatment.

Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity. Recent reports have shown that incidence is much higher than previously assumed and that the majority of patients never achieve full recovery. Traditionally, the diagnosis was mainly based on clinical observations and treatment options were confined to application of corticosteroids and symptomatic management, without proven positive effects on long-term outcomes. These views, however, have been challenged in the last years. Improved imaging methods in MRI and high-resolution ultrasound have led to the identification of structural peripheral nerve pathologies in NA, most notably hourglass-like constrictions. These pathognomonic findings have paved the way for more accurate diagnosis through high-resolution imaging. Furthermore, surgery has shown to improve clinical outcomes in such cases, indicating the viability of peripheral nerve surgery as a valuable treatment option in NA. In this review, we present an update on the current knowledge on this disease, including pathophysiology and clinical presentation, moving on to diagnostic and treatment paradigms with a focus on recent radiological findings and surgical reports. Finally, we present a surgical treatment algorithm to support clinical decision making, with the aim to encourage translation into day-to-day practice.

Backpack palsy and other brachial plexus neuropathies in the military population.

Brachial plexus neuropathy is often seen in the military population, especially due to pressure (backpack palsy, BPP) or idiopathic (neuralgic amyotrophy, NA). We aimed to gain insight in the disease characteristics of soldiers with brachial plexus neuropathies in the Dutch military population and to compare disease characteristics between patients with BPP and NA. In this retrospective chart review study we aimed to include all patients with brachial plexus neuropathy, who presented in the Joint Military Hospital between 1 January, 2011 and 31 December, 2016. We calculated the incidence of NA and BPP and Chi-square tests or Student t tests were performed for differences in patient characteristics between NA and BPP. We included 127 patients, 63 with BPP, 45 with NA, 10 with traumatic brachial plexus neuropathy, and 9 with other plexopathy. The incidence of brachial plexus neuropathy was 50/100 000 person years overall, 25/100 000 person years for BPP, and 18/100 000 person years for NA. Patients in the BPP group differed from the NA with regard to pain (BPP 41% vs NA 93%, P = .000), atrophy (13% BPP vs 29% NA, P = .049), and sensory symptoms (83% BPP vs 44% NA, P = .000). In the BPP group 90% had incomplete recovery and in the NA group 78%. Our study showed a high incidence of BPP and NA in the military population and suggests recovery is not so benevolent as previously thought. Future research is necessary to improve insight and outcome of military patients with brachial plexus neuropathies.

Ventral longitudinal intraspinal fluid collection: Rare presentation as brachial amyotrophy and intracranial hypotension.

CONTEXT: Ventral longitudinal intraspinal fluid collection (VLISFC) presenting as hand amyotrophy has been described only in a few cases and there are no reports on associated intracranial CSF hypovolemia (ICH). We describe the clinical and imaging findings of a case with combined brachial amyotrophy and ICH secondary to VLISFC. FINDINGS: A 31 year old man presented with severe positional neck discomfort, radiating pain, progressive asymmetrical wasting and weakness of distal upper limbs. Contrast Magnetic Resonance Imaging (MRI) of the spine demonstrated a ventral extradural intraspinal fluid collection extending from upper border of C6 to lower border of T3 vertebra with pockets of dorsal collection. Three-dimensional constructive interference in steady state (CISS 3D) used in spinal imaging for identification of CSF leak corroborated with the extent seen on T2 sagittal sections; however, the site of the leak was not identified. After a year he developed disturbing postural headache which was relieved in recumbent position. Follow up MRI of brain was normal while spine demonstrated significant cervical cord atrophy and bilateral cord white matter hyperintensities. Conclusion / Clinical Relevance: We report this unusual case where local compression by VLISFC located at the cervical and upper thoracic level not only caused distal bi-brachial amyotrophy mimicking Hirayama disease but also led to secondary intracranial hypotension. An early identification and intervention could possibly have prevented the onset of ICH.

Phrenic neuropathy and diaphragm dysfunction in neuralgic amyotrophy.

OBJECTIVE: To describe the clinical phenotype and recovery of diaphragm dysfunction caused by neuralgic amyotrophy in a large cohort of patients, to improve accurate awareness of this entity, and to encourage adoption of a standardized approach for diagnosis and treatment. METHODS: This observational cohort study recruited adult patients with neuralgic amyotrophy and symptoms of idiopathic phrenic neuropathy from the database of the Dutch expert center for neuralgic amyotrophy and the Dutch centers for home mechanical ventilation. Demographic and clinical information on diagnosis, symptoms, and recovery was obtained from chart review. We attempted to contact all patients for a follow-up interview. RESULTS: Phrenic neuropathy occurs in 7.6% of patients with neuralgic amyotrophy. Unilateral diaphragmatic dysfunction and bilateral diaphragmatic dysfunction are frequently symptomatic, causing exertional dyspnea, orthopnea, disturbed sleep, and excessive fatigue. Diagnostic practices varied widely and were often not optimally targeted. The majority of patients experienced at least moderate recovery within 2 years. CONCLUSION: We recommend screening every patient with neuralgic amyotrophy for diaphragm dysfunction by asking about orthopnea and by performing upright and supine vital capacity screening and diaphragm ultrasound in cases of suspected phrenic neuropathy to optimize diagnosis and care.

Pathological Cerebrospinal Fluid Findings in Patients With Neuralgic Amyotrophy and Acute Hepatitis E Virus Infection.

There is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV immunoglobulin M occurred in 1 patient, suggesting that HEV is neurotropic.

Clinical phenotype and outcome of hepatitis E virus-associated neuralgic amyotrophy.

OBJECTIVE: To determine the clinical phenotype and outcome in hepatitis E virus-associated neuralgic amyotrophy (HEV-NA). METHODS: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. RESULTS: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12-2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. CONCLUSIONS: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted.

Atypical presentation of Parsonage-Turner syndrome confounded by surgical rotator cuff injury.

Parsonage-Turner syndrome (PTS) is a rare neuropathy that commonly presents as unexpected severe shoulder and arm pain that eventually subsides while weakness or paralysis ensues. During exceptions to this classic presentation, confirming PTS can be challenging. Alternative causes of upper extremity pain may confound the diagnostic algorithm. Moreover, objective findings from necessary diagnostic tests depend on when those tests are performed. We present an atypical onset of PTS, whereby the initial presentation of severe neuropathic pain was preceded by mild shoulder pain that should decrease one's clinical suspicion for PTS. This milder pain coincided with the presence of a rotator cuff injury, whereby surgical intervention preceded impending paralysis and hindered postoperative rehabilitation. Physicians should be aware of the possibility of atypical presentations of PTS in hopes of avoiding either untimely surgery or delays in diagnosis.

Parsonage-Turner syndrome due to autochthonous acute genotype 3f hepatitis E virus infection in a nonimmunocompromised 55-year-old patient.

Hepatitis E virus (HEV) infection is an emerging autochthonous disease in industrialized countries. Extra-hepatic manifestations, in particular neurologic manifestations, have been reported in HEV infection. Only a few cases of hepatitis E-associated Parsonage-Turner syndrome have been reported, and HEV genotypes were rarely determined. Here, we report the case of a Parsonage-Turner syndrome associated with an acute autochthonous HEV infection in a 55-year-old immunocompetent patient. HEV genomic RNA was detected in serum and cerebrospinal fluid samples (CSF), and molecular phylogenetic analysis of HEV was performed. The interest of this case lies in its detailed description notably the molecular analysis of HEV RNA isolated from serum and CSF. HEV infection should be considered in diagnostic investigations of neurologic manifestations associated with liver function perturbations.

Lesion distribution among 281 patients with sporadic neuralgic amyotrophy.

INTRODUCTION: The muscles commonly affected by neuralgic amyotrophy (NA) are well known, but the location of the responsible lesions is less clear (plexus versus extraplexus). METHODS: We report the lesion locations in 281 NA patients as determined by extensive electrodiagnostic (EDX) testing. RESULTS: Our 281 patients had 322 bouts of NA, 57 of which were bilateral, for a total of 379 assessable events. A single nerve was involved in 174 (46%), and 205 (54%) were multifocal. EDX testing identified 703 individual lesions: 699 neuropathies and 4 supraclavicular radiculoplexus lesions. CONCLUSIONS: The frequency of nerve involvement reflects the motor predilection of NA. Involvement of pure motor nerves exceeded that of predominantly motor nerves, both of which far exceeded involvement of more evenly mixed sensorimotor nerves. Cutaneous sensory nerves were least commonly involved. Because of the common C5-C6 innervation, NA often mimics an upper plexus lesion. Extraplexus nerve involvement far exceeded plexus involvement. Distal motor branch involvement explains the severe single-muscle wasting and weakness often observed. Muscle Nerve 55: 858-861, 2017.

MRI bullseye sign: An indicator of peripheral nerve constriction in parsonage-turner syndrome.

INTRODUCTION: The role of MRI in identifying hourglass constrictions (HGCs) of nerves in Parsonage-Turner syndrome (PTS) is largely unknown. METHODS: Six patients with PTS and absent or minimal recovery underwent MRI. Surgical exploration was performed at identified pathologic sites. RESULTS: The time between symptom onset and surgery was 12.4 ± 6.9 months; the time between MRI and surgery was 1.3 ± 0.6 months. Involved nerves included suprascapular, axillary, radial, and median nerve anterior interosseous and pronator teres fascicles. Twenty-three constriction sites in 10 nerves were identified on MRI. A "bullseye sign" of the nerve, identified immediately proximal to 21 of 23 sites, manifested as peripheral signal hyperintensity and central hypointensity orthogonal to the long axis of the nerve. All constrictions were confirmed operatively. CONCLUSIONS: In PTS, a bullseye sign on MRI can accurately localize HGCs, a previously unreported finding. Causes of HGCs and the bullseye sign are unknown. Muscle Nerve 56: 99-106, 2017.