Review of Neurologic Comorbidities in Hospitalized Patients With Opioid Abuse.

PURPOSE OF REVIEW: To determine the prevalence and burden of neurologic comorbidities in hospitalized patients with opioid abuse. RECENT FINDINGS: From 1 year of hospital discharges, 2,182 patients with opioid abuse were identified (prevalence 6.3%), with abuse greater among younger patients (p < 0.0001), women (p < 0.0001), Whites (p < 0.0001), and urban population (p = 0.028). Matching for age, sex, race, and urban-rural residence, 347 patients were reviewed, and 179 (52%) had a neurologic comorbidity. The comorbidities frequently overlapped and included encephalopathy (130), neuromuscular disorders (42), seizures (23), spine disorders (23), strokes (20), CNS infections (3), and movement disorders (2). Abuse patients with neurologic comorbidities experienced substantially greater number of hospital and intensive care unit days and mortality, independent of overdose. SUMMARY: Neurologic comorbidities are a frequent and heretofore underappreciated contributor to the disease burden of hospitalized patients with opioid abuse. The importance of neurologic comorbidities should be included in the public health discussions surrounding the opioid epidemic.

Myotonia permanens with Nav1.4-G1306E displays varied phenotypes during course of life.

INTRODUCTION: Myotonia permanens due to Nav1.4-G1306E is a rare sodium channelopathy with potentially life-threatening respiratory complications. Our goal was to study phenotypic variability throughout life. METHODS: Clinical neurophysiology and genetic analysis were performed. Using existing functional expression data we determined the sodium window by integration. RESULTS: In 10 unrelated patients who were believed to have epilepsy, respiratory disease or Schwartz-Jampel syndrome, we made the same prima facie diagnosis and detected the same heterologous Nav1.4-G1306E channel mutation as for our first myotonia permanens patient published in 1993. Eight mutations were de-novo, two were inherited from the affected parent each. Seven patients improved with age, one had a benign phenotype from birth, and two died of respiratory complications. The clinical features age-dependently varied with severe neonatal episodic laryngospasm in childhood and myotonia throughout life. Weakness of varying degrees was present. The responses to cold, exercise and warm-up were different for lower than for upper extremities. Spontaneous membrane depolarization increased frequency and decreased size of action potentials; self-generated repolarization did the opposite. The overlapping of steady-state activation and inactivation curves generated a 3.1-fold window area for G1306E vs. normal channels. DISCUSSION: Residue G1306 Neonatal laryngospasm and unusual distribution of myotonia, muscle hypertrophy, and weakness encourage direct search for the G1306E mutation, a hotspot for de-novo mutations. Successful therapy with the sodium channel blocker flecainide is due to stabilization of the inactivated state and special effectiveness for enlarged window currents. Our G1306E collection is the first genetically clarified case series from newborn period to adulthood and therefore helpful for counselling.

Near-death experience: arising from the borderlands of consciousness in crisis.

Brain activity explains the essential features of near-death experience, including the perceptions of envelopment by light, out-of-body, and meeting deceased loved ones or spiritual beings. To achieve their fullest expression, such near-death experiences require a confluence of events and draw upon more than a single physiological or biochemical system, or one anatomical structure. During impaired cerebral blood flow from syncope or cardiac arrest that commonly precedes near-death, the boundary between consciousness and unconsciousness is often indistinct and a person may enter a borderland and be far more aware than is appreciated by others. Consciousness can also come and go if blood flow rises and falls across a crucial threshold. During crisis the brain's prime biologic purpose to keep itself alive lies at the heart of many spiritual experiences and inextricably binds them to the primal brain. Brain ischemia can disrupt the physiological balance between conscious states by leading the brainstem to blend rapid eye movement (REM) and waking into another borderland of consciousness during near-death. Evidence converges from many points to support this notion, including the observation that the majority of people with a near-death experience possess brains predisposed to fusing REM and waking consciousness into an unfamiliar reality, and are as likely to have out-of-body experience while blending REM and waking consciousness as they are to have out-of-body experience during near-death.

Blood pressure regulation in diabetic patients with and without peripheral neuropathy.

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.

Does the arousal system contribute to near death experience?

The neurophysiologic basis of near death experience (NDE) is unknown. Clinical observations suggest that REM state intrusion contributes to NDE. Support for the hypothesis follows five lines of evidence: REM intrusion during wakefulness is a frequent normal occurrence, REM intrusion underlies other clinical conditions, NDE elements can be explained by REM intrusion, cardiorespiratory afferents evoke REM intrusion, and persons with an NDE may have an arousal system predisposing to REM intrusion. To investigate a predisposition to REM intrusion, the life-time prevalence of REM intrusion was studied in 55 NDE subjects and compared with that in age/gender-matched control subjects. Sleep paralysis as well as sleep-related visual and auditory hallucinations were substantially more common in subjects with an NDE. These findings anticipate that under circumstances of peril, an NDE is more likely in those with previous REM intrusion. REM intrusion could promote subjective aspects of NDE and often associated syncope. Suppression of an activated locus ceruleus could be central to an arousal system predisposed to REM intrusion and NDE.