The authors reviewed the medical records of 33 patients diagnosed with idiopathic phrenic neuropathy and found that 17 patients had clinical features of neuralgic amyotrophy. They concluded that a careful clinical and electrodiagnostic evaluation may implicate neuralgic amyotrophy as a causative disease in patients with apparently isolated phrenic neuropathy.

Galanin is a peptide hormone widely expressed in the central nervous system and gastrointestinal (GI) tract. Within the GI tract galanin is present in enteric nerve terminals where it is known to modulate intestinal motility by altering smooth muscle contraction. Recent studies also show that galanin can alter intestinal short-circuit current ( I sc) but with differing results observed in rats, rabbits, guinea pigs, and pigs. In contrast, nothing is known about the ability of galanin to alter ion transport in human intestinal epithelial tissues. By RT-PCR, we determined that these tissues express only the galanin-1 receptor (Gal1-R) subtype. To evaluate Gal1-R pharmacology and physiology, we studied T84 cells. Gal1-R expressed by these cells bound galanin rapidly (half time 1–2 min) and with high affinity (inhibitor constant 0.7 ± 0.2 nM). T84 cells were then studied in a modified Ussing chamber and alterations in I sc, a measure of all ion movement across the tissue, were determined. Maximal increases in I sc were observed in a concentration-dependent manner around 2 min after stimulation with peptide, with 1 μM galanin causing I sc to rise more than eightfold and return to baseline occurring within 10 min. The increase in galanin-induced I sc was shown by125I efflux studies to be due to Cl− secretion, which occurred independently of alterations in cAMP and phospholipase C. Rather, Cl− secretion is mediated via a Ca2+-dependent, pertussis toxin-sensitive mechanism. These data suggest that galanin released by enteric nerves may act as a secretagogue in the human colon by activating Gal1-R.

Gastrin-releasing peptide (GRP) is a mitogen and morphogen important in the development of human colon cancers. Although epithelial cells lining the colon do not normally express GRP or its receptor (GRP-R), most human tumors express GRP-R mRNA. Yet functional protein has only been detected in 24 to 40% of colon cancers. To elucidate the reason for the difference between the expression of GRP/GRP-R mRNA and protein, we studied nine human colon cancer cell lines. Quantitative polymerase chain reaction revealed that all colon cancer cell lines expressed similar amounts of mRNA for both GRP as well as GRP-R. Yet binding studies using (125)I-Tyr(4)-bombesin detected functional receptors on only five of the nine cell lines studied. Conformational fragment-length polymorphism analysis indicated that although mRNA for the ligand GRP was never mutated, mRNA for the GRP-R was always mutated. Sequencing revealed that the message for GRP-R contained between two and seven separate mutations at the nucleotide level. This resulted in 14 separate coding mutations, 2 of which were observed in more than one cell line. Each mutation was individually recreated by site-directed mutagenesis and studied in transiently transfected Chinese hamster ovary-K1 cells. Alteration of Pro(145) into a tyrosine, of Val(317) into a glutamic acid, and insertion of a 32-nucleotide segment resulting in a frameshift distal to Asp(137) all resulted in GRP receptors incapable of binding ligand. Thus, these data indicate that human colon cancers commonly express GRP and GRP-R mRNA but that receptor mutations account for the failure of functional protein to be generated.

Traditionally, chronic digital neuropathy of the palmar digital nerve supplying the median aspect of the thumb, caused by perineural fibrosis, has been called a "bowler's thumb." 1,2 Infrequently, a bowler's thumb lesion is a traumatic neuroma caused by the proliferation of fibrous tissues, both around and within the digital nerve. These phenomena are the result of adaptive changes in the thumb in response to frequent insertion and compression in the holes of the bowling ball. 2 The clinical presentation of this condition may include paresthesias, hypesthesia, changes in two-point discrimination sense, or a positive Tinel sign in the distribution of the involved digital nerve, which may be thickened and firm to palpation.This condition is most commonly described in bowling enthusiasts (17/25), 2 although similar involvement can be caused by other sporting activities such as baseball, 3 by repetitive use injuries, 4 and following finger surgery. 2 Treatment for this condition has been both conservative (padding, avoidance of bowling) and surgical (neurolysis, nerve transposition).Case reports. We describe two patients seen in our Electrodiagnostic (EDX) Laboratory after each developed an acute digital neuropathy during a single night of bowling.Patient 1. The first patient was a 41-year-old woman who noted persistent numbness over the medial aspect of her right thumb immediately following 1 hour of bowling. It was the first time she had bowled in many years. She was seen in our EDX Laboratory a few weeks after the onset of symptoms. The median sensory nerve action potential (SNAP) amplitude, elicited from the right thumb, stimulating at the wrist, was 13 V compared with that on the left of 40 V. The right response was abnormal both by laboratory normal values and by comparison with the contralateral side (Ͼ50% difference is considered significant). The remainder of the EDX evaluation, including the amplitude of the median SNAPs bilaterally, recording index finger, and all median SNAP peak latencies, were normal. The patient's symptoms had spontaneously resolved by 2 months following onset.Patient 2. The second patient was a 36-year-old man. He had bowled occasionally but had purchased a new ball with the intention of bowling more frequently. On his first attempts to use this ball, he developed severe pain and paresthesias in the distribution of the right palmar proper digital nerve of the medial aspect of the thumb, which persisted. The EDX assessment, performed 3 weeks following onset, revealed findings similar to the first case (figure). The median SNAP recorded from the right thumb, stimulating median nerve at the wrist, was 14 V, with that on the left at 32 V. All the other EDX results were normal bilaterally, including the median SNAP amplitudes, recording index finger, and all median SNAP latencies. There were no other abnormalities on EDX evaluation. His symptoms resolved spontaneously after 2 months. Neither of these patients had evidence of conditions predisposing them to development of mononeuropathies...

ObjectiveTo describe the efgartigimod treatment regimens and response among 6 US-based patients with generalized myasthenia gravis (gMG) enrolled in an Expanded Access Program (EAP).BackgroundFor some patients with gMG, available therapies do not provide sufficient symptom relief and can cause serious side effects. Efgartigimod, a human IgG1 antibody Fc-fragment (natural ligand of the neonatal crystalline fragment receptor [FcRn]), has increased affinity to FcRn vs endogenous IgG. Efgartigimod reduces IgG recycling and increases IgG degradation. Efgartigimod received FDA approval in 2021 for the treatment of gMG in adults who are anti-acetylcholine receptor (AChR) antibody positive.Design/MethodsIn the efgartigimod EAP (NCT04777734), gMG patients had access to open-label efgartigimod. Eligible patients (=18 y) met clinical criteria of the Myasthenia Gravis Foundation of America classifications II–IV and had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score =5 points (>50% attributed to non-ocular symptoms). During the first two, fixed-treatment cycles, patients received 4 weekly infusions of efgartigimod 10 mg/kg. During the 4-week inter-treatment period, patients received their ongoing treatments and no efgartigimod infusions. Baseline demographic characteristics and safety data were collected. Treating physicians had the option to assess and track clinical function and burden of disease among treated patients.ResultsAs of the cutoff date (Dec 17, 2021), 8 patients have been enrolled in the US; follow-up data are available for 6 (3 males and 3 females; median age 59 y). 83% (5/6) of patients received at least 2 treatment cycles and 4–5 infusions per cycle. Symptom improvements were noted. Four patients reported 6 AEs: fatigue (resolved), tachycardia and headache (both resolved), dyspnea and diplopia (both not resolved), and back spasms (status unknown).ConclusionsWe report on 6 patients with gMG who received efgartigimod as part of an EAP. Detailed patient narratives will be presented.