Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis.

BackgroundLyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected with B. burgdorferi develop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized that B. burgdorferi induces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis.MethodsTo model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune mediators, producer cells, and verified the presence of B. burgdorferi in tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with live B. burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by the in situ TUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC) cultures.ResultsRhesus DRG tissue explants exposed to live B. burgdorferi showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of immune mediators and neuronal apoptosis in a dose dependent manner.ConclusionIn this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.

Myotonia can be treated both pharmacologically and by lifestyle modifications. Cell membrane stabilizers are the medications most commonly used for symptomatic treatment of myotonia. Most patients do not require treatment for the myotonia itself, unless it is severe, but physicians must be aware of anesthesia risks in both myotonia congenita and myotonic dystrophy. A mainstay of management of myotonic dystrophy is the surveillance and treatment of its various systemic complications.

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

IntroductionHuman rabies can be overlooked in places where this disease is now rare. Its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a Guillain-Barré syndrome (GBS) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (ABN).Case presentationA 19-year-old Mexican, with no past health problems, presented with a two-day history of left shoulder, arm, and chest pain. He arrived in Louisiana from Mexico five days prior to admission. Of particular importance is the absence of a history of rabies exposure and immunization. On admission, the patient had quadriparesis, areflexia, and elevated protein in the cerebrospinal fluid, prompting a diagnosis of GBS. However, emerging neurological deficits pointed towards acute encephalitis. Rabies was suspected on hospital day 11 after common causes of encephalitis (eg, arboviruses) have been excluded. The patient tested positive for rabies IgM and IgG. He died 17 days after admission. Negri bodies were detected in the patient’s brain and rabies virus antigen typing identified the vampire bat as the source of infection.ConclusionRabies should be suspected in every patient with a rapidly evolving GBS-like illness—even if there is no history of exposure and no evidence of encephalitis on presentation. The patient’s ABN-like symptoms may be equivalent to the pain experienced by rabies victims near the inoculation site.

IntroductionTypical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE “de novo” in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury.Case presentationA 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour).ConclusionThis is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, ‘post-hypoxic’ TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.