Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat.

The nucleus accumbens (NAc) receives cortical projections principally from the insular cortex (IC) and medial prefrontal cortex (mPFC). Among NAc neurons, cholinergic interneurons (ChNs) regulate the activities of medium spiny neurons (MSNs), which make up ~ 95% of NAc neurons, by modulating their firing and synaptic properties. However, little is known about the synaptic mechanisms, including their cell-type-dependent corticoaccumbal projection properties and cholinergic effects on the NAc core. Here, we performed whole-cell patch-clamp recordings from NAc MSNs and ChNs in acute brain slice preparations obtained from rats that received an AAV5-hSyn-ChR2(H134R)-mCherry injection into the IC or mPFC. Light stimulation of IC or mPFC axons induced comparable phase-locked excitatory postsynaptic currents (EPSCs) in MSNs. On the other hand, ChNs showed consistent EPSCs evoked by light stimulation of mPFC axons, whereas light stimulation of IC axons evoked much smaller EPSCs, which often showed failure in ChNs. Light-evoked EPSCs were abolished by tetrodotoxin and were recovered by 4-aminopyridine, suggesting that corticoaccumbal projections monosynaptically induce EPSCs in MSNs and ChNs. Carbachol effectively suppressed the amplitude of EPSCs in MSNs and ChNs evoked by light stimulation of IC or mPFC axons and in ChNs evoked by stimulating mPFC axons. The carbachol-induced suppression was recovered by atropine or pirenzepine, while preapplication of gallamine, J104129, PD102807, or AF-DX384 did not block the carbachol-induced EPSC suppression. These results suggest that NAc MSNs and ChNs are differentially regulated by excitatory projections from the IC and mPFC and that these corticoaccumbal excitatory inputs are modulated by M1 receptor activation.

ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

BACKGROUND: Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. RESULTS: The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. CONCLUSIONS: These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying.

p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.

BACKGROUND: Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. RESULTS: Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1ß over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. CONCLUSIONS: These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

Functional roles of descending projections from the cerebral cortex to the trigeminal spinal subnucleus caudalis in orofacial nociceptive information processing.

BACKGROUND: The trigeminal spinal subnucleus caudalis (Sp5C), also known as the medullary dorsal horn, receives orofacial somatosensory inputs, particularly nociceptive inputs, from the trigeminal nerve. In the Sp5C, excitatory and inhibitory neurons, glutamatergic and GABAergic/glycinergic neurons, respectively, form the local circuits. The axons of the glutamatergic neurons in lamina I ascend toward the thalamic and parabrachial nuclei, and this projection is the main pathway of orofacial nociception. Additionally, the axons of the higher brain regions, including the locus coeruleus, dorsal raphe, and cerebral cortex, are sent to the Sp5C. HIGHLIGHT: Among these descending projections, this review focuses on the functional profiles of the corticotrigeminal projections to the Sp5C, along with their anatomical aspects. The primary and secondary somatosensory and insular cortices are of particular interest. CONCLUSION: Corticotrigeminal projections from the somatosensory cortex to the Sp5C play a suppressive role in nociceptive information processing, whereas recent studies have demonstrated a facilitative role of the insular cortex in nociceptive information processing at the Sp5C level.

Pure Motor Isolated Finger Palsy by Cerebral Infarction: Tips for Diagnosis by Neurological Examination.

There are various causes of unilateral finger palsy. Its potential etiologies include peripheral neuropathy, carpal tunnel syndrome, and nerve root disorder due to myelopathy. In addition to them, similar paralysis has been reported in localized lesions of the cerebrum, classically referred to as pseudoperipheral palsy. In this report, we describe a case of an 80-year-old man who developed sudden clumsiness of the right fingers. Neurological examination showed muscle weakness mainly in the 1st and 2nd fingers (Medical Research Council grade 1-4) and normal reflexes in the extremities. The affected muscles were innervated by the median nerve, ulnar nerve, and radial nerve, and their nerve root levels ranged from C6 to T1. All the Phalen's, Tinel's, and flick signs were negative. Diffusion-weighted brain magnetic resonance imaging showed hyperintensity limited in the precentral knob on the left precentral gyrus. The etiology was diagnosed as cardiogenic embolism due to atrial fibrillation. In this report, we provide key findings for diagnosing pure motor isolated finger palsy by cerebral infarction through neurological examination.

A Case of Autoimmune Polyendocrine Syndrome Type 3B and Peripheral Neuropathy Due to Thiamine Deficiency.

Autoimmune polyendocrine syndrome (APS) type 3B is characterized by presence of autoimmune thyroid disease, chronic atrophic gastritis and pernicious anemia. In this report, we present a rare case of APS type 3B with neuropathy by thiamine deficiency. A 65-year-old man had a history with hypothyroidism, gastritis, gastrectomy for gastric cancer and subacute combined degeneration of the spinal cord. Patient developed polyneuropathy with not mecobalamin but thiamine deficiency. Serum anti-thyroglobin (TG), anti-thyroid peroxidase (TPO), and anti-gastric parietal cell antibodies were positive. He was treated with thiamine supplementation and improved muscle weakness, sensory impairment and gait disturbance. Classically, it is reported gastric cancer related to hypothyroidism. Additionally, thiamine deficiency can be caused by gastrectomy. Here, his thiamine deficiency was related to APS type 3B, leading to polyneuropathy.

Double Skull Sign After Cranioplasty: A Case Report.

The double skull sign (DSS) is a unique image on the outside of the brain that looks like two skulls. Whereas congenital and acquired types of DSS have been reported, the etiology of both of them is calcified hematomas. We encountered a case of a 46-year-old woman with a history of subarachnoid hemorrhage followed by cranioplasty at 43 years old. She developed right hemiparalysis and motor aphasia suddenly. Brain computed tomography and magnetic resonance imaging revealed not only cerebral infarction but also DSS incidentally. After detailed analysis, we concluded that the DSS in this case was not due to calcification of the hematoma but was related to the cranioplasty. In this report, we present an interesting case and discuss etiologies of the development of DSS after cranioplasty.

Dural Arteriovenous Fistula in Neuro-Behçet's Disease: Association or Chance?

Behçet's disease (BD) is a multisystemic vasculitis disorder. Neuro-Behçet's disease (NBD) is a set of neurologic symptoms imputable to an underlying Behçet vasculitis. Among the wide range of vascular abnormalities secondary to BD, a dural arteriovenous fistula (dAVF) is not classically described. Whether a dAVF is associated with BD or dAVF is a chance occurrence is still a matter of debate. Herein, we describe an NBD case of a 48-year-old male, presenting with headache and fever, where a dAVF was seen on imaging. He was treated with prednisolone and colchicine, followed by the surgical resection for dAVF. Then, we discuss the possible association between BD and dAVF based on the latest literature.

Lateral Medullary Infarction With Atonic Bladder and Lateropulsion.

Lateral medullary infarction (LMI), or Wallenberg syndrome, can develop various symptoms, but it is rare that ipsilateral axial lateropulsion (or body lateropulsion, BL) or atonic bladder (AB) are caused by LMI. This report describes a case of LMI with both BL and AB. A 77-year-old man, with a history of hypertension and diabetes, developed acute left BL and anuresis. A neurological exam showed right gaze nystagmus, slight dysarthria and dysphagia, right dysesthesia in the trunk, and ataxia in the left limbs and trunk. Horner's syndrome and paralysis were unremarkable. Brain magnetic resonance imaging revealed hyperintensity in the lateral medulla oblongata. Cystometry revealed AB, although the patient had the urge to urinate. Owing to acute therapy, although trunk ataxia was presented for several months, BL and anuresis were recovered on day 15 and day 35, respectively. Here, we describe the potential mechanisms of BL and AB caused by LMI.

Efficacy of Trihexyphenidyl on Apraxia of Eyelid Opening in Parkinsonism: A Case Report.

Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by Parkinsonism. In this report, we describe a case of AEO in Parkinsonism improved by trihexyphenidyl (THP). The patient was a 64-year-old woman, who was previously healthy but developed bradykinesia. She was clinically diagnosed as PD due to an L-dopa challenge test, but no other detailed tests were performed. She started antiparkinsonian medications and her symptoms were improved at an early phase. However, her motor symptoms were gradually exacerbated over time, and antiparkinsonian medications were dosed up. At 69 years old, blepharospasm and AEO developed. Although other antiparkinsonian medications did not improve her AEO, THP cured AEO dramatically at 73 years old. In this report, we discuss a mechanism of AEO by Parkinsonism and the pathway of THP for the improvement of AEO.

Miller-Fisher Syndrome Following Influenza A Infection.

Miller-Fisher syndrome (MFS), characterized by ophthalmoplegia, ataxia, and areflexia, is a Guillain-Barré syndrome (GBS) variant. It is well-known that the causative antibody for MFS is anti-GQ1b antibody. This report describes a rare case of MFS with not only anti-GQ1b antibodies but also anti-GT1a antibodies following Influenza A infection. The patient, a 47-year-old woman, contracted Influenza A three weeks before admission. She complained of double vision followed by areflexia, ataxia in the four extremities, and complete gaze palsy. She was treated with intravenous methylprednisolone pulse and intravenous immunoglobulin therapies. Her neurological symptoms were recovered after these immunotherapies.

Is it safe to control the car pedal with the lower limb of the unaffected side in patients with stroke?

OBJECTIVES: Few studies have examined motor function in determining the suitability of patients with stroke to resume driving a car. Patients with hemiplegia usually control car pedals with the unaffected lower limb. However, motor control on the unaffected side is also impaired in patients with stroke. This study aimed to clarify the neurophysiological characteristics of pedal switching control during emergency braking in patients with hemiplegia. METHODS: The study participants consisted of 10 drivers with left hemiplegia and 10 age-matched healthy drivers. An experimental pedal was used to measure muscle activity and kinematic data during braking, triggered by the light from a light-emitting diode placed in front of the drivers. RESULTS: The patient group took the same reaction time as the healthy group. However, from the visual stimulus to the release of the accelerator pedal, the patient group had higher muscle activity in the tibialis anterior and rectus femoris and had faster angular velocities of hip and knee flexion than the healthy group. In addition, the patient group had higher co-contraction activities between flexors and extensors. From the accelerator pedal release to brake contact, the patient group had slower angular velocities of hip adduction, internal rotation, ankle dorsiflexion, internal return, and internal rotation than the healthy group. CONCLUSIONS: Patients with hemiplegia exhibited poor control of pedal switching using their unaffected side throughout the pedal-switching task. These results indicate that the safety related to car-pedal control should be carefully evaluated while deciding whether a patient can resume driving a car after a stroke.

Normal-Pressure Hydrocephalus-Like Appearance in Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is one of the monogenic neurological diseases that neurologists most often experience. DM1 can develop several symptoms, including muscle weakness, gait disturbance, urinary incontinence, and cognitive decline. Other hand, normal pressure hydrocephalus (NPH) is more frequent in the elderly population and is characterized by a triad of symptoms, gait disturbance, urinary urge incontinence, and cognitive decline. Therefore, some symptoms overlap between DM1 and NPH. In this report, we described a case of DM1 that presented with a triad of NPH, and NPH-like changes in brain images. A 54-year-old man with DM1 visited our hospital for rehabilitation. He had a history of dyslipidemia, diabetes, and cataracts. He developed muscle weakness, blepharoptosis, and dysarthria at 43 years. Neuro-exam revealed percussion and grip myotonia, distal muscle weakness and atrophy, broad-based gait, and urinary incontinence. The mini-mental state examination score was 18. Brain magnetic resonance imaging revealed enlarged lateral and third ventricles and Evans index was 0.38 (NPH criterion; >0.3), which was mimicking for NPH. Tap test (TT) was evaluated twice. First TT improved clinical symptoms slightly, but second was unremarkable. Based on the second TT result, we could not diagnose with NPH and could prevent unnecessary surgical shunting. Brain imaging of DM1 can show an NPH-like appearance in patients older than 50. Although TT is the gold standard for diagnosing NPH, its sensitivity and specificity vary among reports. TT results should be interpreted with caution before performing a surgical shunt. If necessary, multiple TTs should be considered in DM1 patients.

Treatment of Subcortical Aphasia Due to Putaminal Hemorrhage With the Japanese Version of Melodic Intonation Therapy (MIT-J).

Melodic intonation therapy (MIT) is one of the rehabilitation methods for patients with non-fluent or dysfluent aphasia, mainly caused by stroke or brain injury. Although MIT is conducted in various languages, reports on the Japanese version of MIT (MIT-J) are limited. In this report, we describe a case about the efficacy of MIT-J in the subacute phase after stroke on subcortical aphasia. Our case was a 60-year-old right-handed woman who suffered from left putaminal hemorrhage. She was treated with acute therapy, including medications and rehabilitation, but non-fluent aphasia was preserved. Regardless of general speech therapies, her aphasia was not improved. In the subacute phase, we started MIT-J (protocol: 20 minutes per day, five days per week for two weeks). The effect of MIT-J was remarkable and in particular, speech intelligibility was improved. It is required to accumulate more cases to reveal the effect of MIT-J.

Stellate ganglion block as an early intervention in sympathetically maintained headache and orofacial pain caused by temporal arteritis.

INTRODUCTION: We report a case of temporal arteritis with a sympathetic component in the orofacial region, which responded to stellate ganglion blocks (SGBs). CASE: An 81-year-old woman with limited mouth opening and pain upon chewing was referred to the Orofacial Pain Clinic at Nihon University Dental Hospital. The patient also presented with blurred vision and a burning sensation on the right side of her face. On clinical examination, the temporal artery was tender to palpation, and there was increased sensitivity in the temporal region bilaterally. The patient reported jaw pain and limited mouth opening. Laboratory examination showed elevations in erythrocyte sedimentation rate and C-reactive protein. The burning sensation was due to a sympathetic component, and SGBs substantially reduced both the burning sensation and right temporal pain. Blocking the sympathetic chain on the ipsilateral side also improved jaw movement. The patient was referred to a rheumatologist, after which she was admitted to hospital with a tentative diagnosis of temporal arteritis. Treatment with oral prednisone 30 mg daily was initiated, and the dose was tapered as her symptoms resolved. DISCUSSION: The reason for the gradual pain relief after SGB is unclear, but we believe it was effective for ischemia in temporal arteritis because it led to dilation of affected arteries or suppression of inflammation/edema of the vascular wall. CONCLUSION: This case demonstrates that SGB may relieve pain related to temporal arteritis and sympathetically maintained headache and orofacial pain by reducing noxious stimulation peripherally and decreasing central pain transmission centrally.

Descending projections from the insular cortex to the trigeminal spinal subnucleus caudalis facilitate excitatory outputs to the parabrachial nucleus in rats.

ABSTRACT: Nociceptive information from the orofacial area projects to the trigeminal spinal subnucleus caudalis (Sp5C) and is then conveyed to several nuclei, including the parabrachial nucleus (PBN). The insular cortex (IC) receives orofacial nociceptive information and sends corticofugal projections to the Sp5C. The Sp5C consists of glutamatergic and GABAergic/glycinergic interneurons that induce excitatory postsynaptic currents and inhibitory postsynaptic currents, respectively, in projection neurons. Therefore, quantification of glutamatergic IC inputs in combination with identifying postsynaptic neuronal subtypes is critical to elucidate IC roles in the regulation of Sp5C activities. We investigated features of synaptic transmission from the IC to glutamatergic and GABAergic/glycinergic Sp5C neurons of laminae I/II using vesicular GABA transporter-Venus transgenic rats that received an injection of adeno-associated virus-channelrhodopsin-2-mCherry into the IC. Selective stimulation of IC axon terminals in Sp5C slice preparations induced monosynaptic excitatory postsynaptic currents in both excitatory glutamatergic and inhibitory GABAergic/glycinergic Sp5C neurons with a comparable amplitude. Paired whole-cell patch-clamp recordings showed that unitary inhibitory postsynaptic currents from inhibitory neurons influencing excitatory neurons, including neurons projecting to the PBN, exhibited a high failure rate and were suppressed by both bicuculline and strychnine, suggesting that excitatory neurons in the Sp5C receive both GABAergic and glycinergic inhibition with low impact. Moreover, selective stimulation of IC axons increased the firing rate at the threshold responses. Finally, we demonstrated that selective stimulation of IC axons in the Sp5C by a chemogenetic approach decreased the thresholds of both mechanical and thermal nociception. Thus, IC projection to the Sp5C is likely to facilitate rather than suppress excitatory outputs from the Sp5C.

Insular cortical descending projections facilitate neuronal responses to noxious but not innoxious stimulation in rat trigeminal spinal subnucleus caudalis.

The insular cortex (IC) receives orofacial nociceptive information. Pyramidal neurons in IC layer V send their axons to various brain regions, such as the trigeminal spinal subnucleus caudalis (Sp5C), parabrachial nucleus, and periaqueductal gray. However, little information has been available about the functions of these descending projections from the IC. This study aimed to elucidate the effect of IC â†’ Sp5C on neuronal spike firings responding to noxious and innoxious stimuli to the face of the rat receiving an injection of adeno-associated virus encoding modified channelrhodopsin-2 (ChR2) fused to mCherry under the control of the human synapsin promotor. We classified Sp5C neurons responding to mechanical stimuli into three groups: low-threshold (LT), nociceptive specific (NS), and wide dynamic range (WDR) neurons, which respond to innoxious stimuli (brushing) only, noxious mechanical stimuli (pinching) only, and both noxious and innoxious stimuli, respectively. Neuronal activities of IC neurons were activated by photostimulation (repetitive pulses at 20 Hz for 5 Hz) to the IC that consistently induced action potentials in IC layer V pyramidal neurons. LT neurons showed comparable spike firing rates to brushing the facial skin before and during ChR2 activation induced by photostimulation. In contrast, NS neurons showed an increase in their firing frequency to pinching during ChR2 activation. On the other hand, WDR neurons increased their Sp5C neuronal firing to pinching during ChR2 activation without changing their firing rates to innoxious mechanical stimuli. These results suggest that the IC descending projections facilitate nociception by increasing Sp5C neuronal activities responding to noxious mechanical stimuli.

Insulin facilitates synaptic transmission via gap junctions between fast-spiking interneurons in the rat insular cortex.

PURPOSE: Inhibitory synaptic currents from fast-spiking neurons (FSNs), a typical gamma-aminobutyric acid (GABA)ergic interneuron in the cerebral cortex, to pyramidal neurons are facilitated by insulin. FSNs frequently show electrical synapses to FSNs, however, the effect of insulin on these electrical synapses is unknown. The aim of this study was to evaluate effects of insulin on electrical synaptic potentials between FSNs. METHODS: Electrical synaptic potentials via gap junctions between FSNs were recorded to examine how insulin modulates these potentials in the rat insular cortex (IC). RESULTS: Bath application of insulin (10 nM), which increases the spike firing rate of pyramidal neurons and unitary inhibitory postsynaptic currents recorded from FSN to pyramidal neuron connections, slightly but significantly increased electrical synaptic currents. The mean ratio of electrical synapses, the coupling coefficient that is obtained by postsynaptic voltage responses divided by presynaptic voltage amplitude, was 8.3 ± 1.1% in control and 9.2 ± 1.1% (n = 14) during 10 nM insulin application. Input resistance and voltage responses to large hyperpolarizing currents (-140 pA) were not changed by insulin. CONCLUSION: These results suggest that insulin facilitates spike synchronization by increasing electrical synaptic currents via gap junctions of GABAergic FSNs in the IC.

Insulin potentiates inhibitory synaptic currents between fast-spiking and pyramidal neurons in the rat insular cortex.

Insulin plays roles in brain functions such as neural development and plasticity and is reported to be involved in dementia and depression. However, little information is available on the insulin-mediated modulation of electrophysiological activities, especially in the cerebral cortex. This study examined how insulin modulates the neural activities of inhibitory neurons and inhibitory postsynaptic currents (IPSCs) in rat insular cortex (IC; either sex) by multiple whole-cell patch-clamp recordings. We demonstrated that insulin increased the repetitive spike firing rate with a decrease in the threshold potential without changing the resting membrane potentials and input resistance of fast-spiking GABAergic neurons (FSNs). Next, we found a dose-dependent enhancement of unitary IPSCs (uIPSCs) by insulin in the connections from FSNs to pyramidal neurons (PNs). The insulin-induced enhancement of uIPSCs accompanied decreases in the paired-pulse ratio, suggesting that insulin increases GABA release from presynaptic terminals. The finding of miniature IPSC recordings of the increased frequency without changing the amplitude supports this hypothesis. Insulin had little effect on uIPSCs under the coapplication of S961, an insulin receptor antagonist, or lavendustin A, an inhibitor of tyrosine kinase. The PI3-K inhibitor wortmannin or the PKB/Akt inhibitors, deguelin and Akt inhibitor VIII, blocked the insulin-induced enhancement of uIPSCs. Intracellular application of Akt inhibitor VIII to presynaptic FSNs also blocked insulin-induced enhancement of uIPSCs. In contrast, uIPSCs were enhanced by insulin in combination with the MAPK inhibitor PD98059. These results suggest that insulin facilitates the inhibition of PNs by increases in FSN firing frequency and IPSCs from FSNs to PNs. (250 words).

Case report: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion: an autopsy case.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion is a clinicoradiological syndrome characterized by transient neuropsychiatric symptoms and hyperintensity of the splenium of the corpus callosum on diffusion-weighted MRI. Although intramyelinic edema and inflammatory cell infiltration can be predicted by MRI, the pathology of the splenium of the corpus callosum remains unknown. We encountered a case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion and hypoglycemia in a patient who died of sepsis, and an autopsy was performed. The postmortem pathological findings included intramyelinic edema, myelin pallor, loss of fibrous astrocytes, microglial reactions, and minimal lymphocytic infiltration in the parenchyma. Based on these findings, transient demyelination following cytotoxic edema in the splenium of corpus callosum was strongly considered a pathogenesis of "clinically mild encephalitis/encephalopathy with a reversible splenial lesion" associated with hypoglycemia, and it could be generalized for the disease associated with the other causes. As cytotoxic edema could be the central pathology of the disease, the recently proposed term cytotoxic lesions of the corpus callosum may be applicable to this syndrome.