Limited bedding and nesting increases ethanol drinking in female rats.

Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α1-adrenoceptor density and decrease α2-adrenoceptor density in brain to confer a stress-responsive phenotype. Pregnant rats received morphine (15 mg/kg/day) or saline via subcutaneous minipumps from gestational day 9 until birth. Limited bedding and nesting (LBN) procedures were introduced from postnatal day (PD) 3-11 to mimic early life adversity-scarcity. Offspring rats (PD 31-33) were given opportunities to drink EtOH (20 %, v/v) using intermittent-access, two-bottle choice (with water) procedures. Rats given access to EtOH were assigned into sub-groups that were injected with either yohimbine (1 mg/kg, ip) or vehicle (2 % DMSO, ip) 30 min prior to each EtOH access session to determine the effects of α2-adrenoceptor inhibition on alcohol drinking. We harvested cortices, brainstems, and hypothalami from EtOH-naïve littermates on either PD 30 or PD 70 and conducted radioligand receptor binding assays to quantify α1- and α2-adrenoceptor densities. Contrary to our hypothesis, only LBN alone increased EtOH intake in female adolescent rats compared to female rats with POE. Neither POE nor LBN affected α1- or α2-adrenoceptor densities in the cortex, brainstem, or hypothalamus of early- or late-aged adolescent rats. These results suggest a complex interaction between ELA type and sex on alcohol drinking.

Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial.

OBJECTIVE: B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis (MS). This study sought to evaluate the efficacy, safety, and tolerability of add-on therapy with rituximab, a monoclonal antibody that depletes circulating B cells, in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity (Class III evidence). METHODS: Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent, and with at least 1 gadolinium-enhancing (GdE) lesion on any of 3 pretreatment MRIs, received rituximab administered at 375 mg/m(2) weekly x 4 doses. Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion. Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were obtained at baseline and throughout the posttreatment follow-up. RESULTS: GdE lesions were reduced after treatment with rituximab, with 74% of posttreatment MRI scans being free of GdE activity compared with 26% free of GdE activity at baseline (p < 0.0001). Median GdE lesions were reduced from 1.0 to 0, and mean number was reduced from 2.81 per month to 0.33 after treatment (88% reduction). MSFC improved as well (p = 0.02). EDSS remained stable. CONCLUSION: Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study. In combination with standard injectable therapies, rituximab was well-tolerated with no serious adverse events. B-cell-modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to standard injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis.

Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses.

BACKGROUND: The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses to control NDV and spouses. METHODS: The authors performed standardized neurologic examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who previously participated in a national mail and telephone survey. Presence of DSP was evaluated by history, physical examination, and standardized electrophysiologic assessment of motor and sensory nerves. Similar examinations were performed without electrophysiologic tests in 484 DV spouses and 533 NDV spouses. Statistical analyses were performed with appropriate adjustments for the stratified sampling scheme. RESULTS: No differences between adjusted population prevalence of DSP in DV and NDV were found by electrophysiology (3.7% vs 6.3%, p = 0.07), by neurologic examination (3.1% vs 2.6%, p = 0.60), or by the methods combined (6.3% vs 7.3%, p = 0.47). Excluding veterans with non-military service related diseases that may cause DSP did not alter outcomes. DV potentially exposed to neurotoxins from the Khamisiyah ammunition depot explosion did not significantly differ in DSP prevalence compared to non-exposed DV. The prevalence of DSP in DV spouses did not differ from NDV spouses (2.7% vs 3.2%, p = 0.64). CONCLUSIONS: Neither veterans deployed during the Gulf War era nor their spouses had a higher prevalence of DSP compared to NDV and spouses.

"Fou rire prodromique" as the presentation of pontine ischaemia secondary to vertebrobasilar stenosis.

"Fou rire prodromique" (prodrome of crazy laughter) is a rare form of pathological laughter of uncertain pathophysiology. A patient is presented with pathological laughter as the first manifestation of pontine ischaemia due to vertebrobasilar stenosis. A 65 year old man developed uncontrollable and unemotional laughter for almost an hour followed by transient right facial-brachial paresis. He had fluctuation of laughter, right facial brachial paresis, and occasional crying. Magnetic resonance imaging, magnetic resonance angiogram (MRA), and an angiogram showed small left pontine and cerebellar infarcts, left vertebral artery occlusion, and right vertebral and basilar artery stenosis. His condition deteriorated to bilateral brain stem infarction and he died. Necropsy confirmed the extensive brain stem infarction. Pathological laughter can be the very first presenting manifestation of ischaemia of the ventrotegmental junction of the upper pons. It is hypothesised that the pathological laughter in this patient was secondary to ischaemic ephaptic stimulation of the descending corticopontine/ bulbar pathways.

Polyneuropathies associated with high titre antisulphatide antibodies: characteristics of patients with and without serum monoclonal proteins.

OBJECTIVES: Previous studies of small numbers of patients have shown that antisulphatide autoantibodies are associated with polyneuropathies having a prominent sensory component. However, clinical and electrodiagnostic features are variable. The range of clinical and electrodiagnostic findings in 19 patients with polyneuropathies and high titre (> 4500) serum IgM antisulphatide antibodies is described, together with testing for serum monoclonal (M) proteins. METHODS: About 20000 serum samples that were referred to the clinical laboratory from 1990 to the end of 1994 were screened by enzyme linked immunosorbent assay (ELISA) for specific high titre antisulphatide antibodies. The clinical and electrodiagnostic data in 23 patients with positive results were reviewed. IgM binding to peripheral nerve structures was also evaluated in these patients. RESULTS: Nineteen patients had predominantly distal, symmetric pansensory loss. Patients with IgM antisulphatide antibodies and no serum M protein usually had clinical syndromes that included: (1) neuropathic pain or dysaesthesiae, (2) no functionally significant weakness, and (3) an axonal neuropathy on electrodiagnostic testing. On immunocytochemical studies serum IgM from the patients without M proteins usually (nine of 10; 90%) bound to peripheral nerve axons, but never to myelin. Patients with antisulphatide antibodies and a serum M protein, usually IgM, were more likely than patients without a serum M protein, to have syndromes with: (1) no pain or dysaesthesiae, (2) motor abnormalities, and (3) a demyelinating polyneuropathy by electrodiagnostic criteria. In immunocytochemical studies serum IgM most often bound to either peripheral nerve myelin or endoneurial structures. CONCLUSION: Patients with polyneuropathy and high titre serum IgM antisulphatide antibodies can be classified into subgroups according to the presence or absence of a serum M protein. Patients without an M protein are more likely to have pure sensory syndromes, pain, an axonal neuropathy, and serum IgM binding to axons. Patients with a serum M protein commonly had syndromes with prominent motor involvement, no pain, and a demyelinating neuropathy.

Nerve root hypertrophy as the cause of lumbar stenosis in chronic inflammatory demyelinating polyradiculoneuropathy.

Two patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) developed signs of lumbar stenosis. Radiologic, intraoperative, and pathologic findings demonstrated lumbar stenosis secondary to nerve root hypertrophy. This syndrome has been demonstrated in hereditary but not acquired demyelinating neuropathies. CIDP should be considered in the differential diagnosis of sciatica and nerve root hypertrophy.

Chronic sesamoiditis of the thumb: pathomechanics and treatment.

Entrapment of the sesamoids within the metacarpophalangeal joint can result in irreducible dislocations; however, dysfunction from trauma-induced, chronic sesamoiditis is unfamiliar. Twenty-five patients with intractable posttraumatic pain of the metacarpophalangeal joint of the thumb are reported. The mechanisms of the palmar plate injury included hyperextension, direct compression, shear forces, and lateral stress. Sesamoidectomy achieved good results in 80% of patients as evidenced by return to preinjury activities. Residual joint stiffness was present in 20% of patients, and 8% had significant residual pain. Traumatic microtears appear to produce pathologic findings in the perisesamoid tendon and/or sesamoid-metacarpal articulation.

The use of Hexcelite in splinting the thumb.

Hexcelite Orthopaedic Tape can be used effectively for splinting thumb joints. The open weave material is easily molded, lightweight, and durable. It is useful in the rehabilitation management of a variety of thumb disorders and is well accepted by patients.

Medical and surgical importance of the arterial blood supply of the thumb.

The arterial supply of the thumb was studied in 50 cadaver hands. In 80% the princeps pollicis artery was the first palmar metacarpal artery, a major branch of the deep radial arch. In 50% of the specimens the princeps pollicis artery also supplied the proper radial digital artery to the index finger. Variations of the thumb arterial patterns were present in 25%. In 75% there was a single end-arterial blood supply to the thumb. The anatomic findings are correlated with problems of radial artery injections, thrombosis, and surgical injury to illustrate the clinical importance of the princeps pollicis artery.