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Objective: Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI)., Methods: A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262)., Results: Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs)., Conclusion: ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs., (© 2024. The Author(s).)

Background: The novel COVID-19 vaccines have side effects that require efficient and close monitoring., Aims of the Study: To examine whether the Pfizer-BioNTech vaccine is associated with multiple cranial neuropathy., Methods: We report the case of a 29-year-old male patient with no notable history who presented with left oculomotor, abducens, trigeminal and facial palsies 6 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine., Results: Gadolinium-enhanced MRI of the brain revealed enhancement in the left facial, trigeminal and oculomotor nerves, which persisted upon repeated examination. The cerebrospinal fluid analysis showed no sign of inflammation, both initially and after 1 month from the start of the patient's symptoms. Other causes were excluded by laboratory tests. The patient received high doses of corticosteroids, with improvement of symptoms., Conclusions: In our case, the most probable etiology of the patient's multiple cranial neuropathy is the Pfizer-BioNTech vaccine, which highlights the need for prolonged surveillance of COVID-19 vaccine neurological complications., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To describe the spectrum, treatment, and outcome of cranial nerve disorders associated with immune checkpoint inhibitor (Cn-ICI)., Methods: This nationwide retrospective cohort study on Cn-ICI (2015-2019) was conducted using the database of the French Refence Center. In addition, a systematic review of the literature (MEDLINE, Scopus, and Web of Science) for records published between 2010 and 2019 was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the search terms cranial nerve or neuropathy or palsy and immune checkpoint inhibitors., Results: Among 67 cases with ICI-related neurologic toxicities diagnosed in our reference center, 9 patients with Cn-ICI were identified (7 men, 78%, median age 62 years [range 26-82 years]). Patients were receiving a combination of anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death 1 (PD-1)/PD-1 ligand (n = 5, 56%) or anti-PD-1 antibodies alone (n = 4, 44%). Cn-ICI involved optic (n = 3), vestibulocochlear (n = 3), abducens (n = 2), facial (n = 2), and oculomotor (n = 1) nerves. Two patients had involvement of 2 different cranial nerves. Treatment comprised corticosteroids (n = 8, 89%), ICI permanent discontinuation (n = 7, 78%), plasma exchange (n = 2, 22%), and IV immunoglobulin (n = 1, 11%). Median follow-up was 11 months (range 1-41 months). In 3 cases (33%), neurologic deficit persisted/worsened despite treatment: 2 optic and 1 vestibulocochlear. Among cases from the literature and the present series combined (n = 39), the most commonly affected cranial nerves were facial (n = 13, 33%), vestibulocochlear (n = 8, 21%), optic (n = 7, 18%), and abducens (n = 4, 10%). Trigeminal, oculomotor, and glossopharyngeal nerves were less frequently affected (total n = 7)., Conclusion: Cranial nerve disorders can complicate treatment with ICIs. Approximately one-third of the patients had persisting deficits, most frequently involving hearing and vision loss., (© 2020 American Academy of Neurology.)

Objective: While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma., Methods: Patients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the ClearPoint imaging software., Results: Seven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean ± SD]: 2.66 ± 0.35 vs 2.42 ± 0.75; p = 0.45)., Conclusions: This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.

Acrylamide (ACR) is a potent neurotoxin that can be produced during high-temperature food processing, but the underlying toxicological mechanism remains unclear. In this study, the detrimental effects of ACR on the striatal dopaminergic neurons and the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) in ACR-induced neuronal apoptosis were investigated. Acute ACR exposure caused dopaminergic neurons loss and apoptosis as revealed by decreased tyrosine hydroxylase (TH)-positive cells and TH protein level and increased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the striatum. ACR-decreased glutathione content, increased levels of malondialdehyde, proinflammatory cytokines tumor necrosis factor α, and interleukin 6. In addition, nuclear NF-κB and MAPKs signaling pathway with c-Jun N-terminal kinase (JNK) and p38 were activated by ACR. Specific inhibitors were used to explore the roles of MAPKs and NF-κB pathways in ACR-induced apoptosis in SH-SY5Y cells. Pretreatment with JNK-specific inhibitors SP600125 markedly upregulated the reduced B-cell lymphoma 2 (Bcl-2) content and downregulated the increased Bcl-2-associated X protein (Bax) level and thereby eventually reduced the proportions of early and late apoptotic cells induced by ACR, while p38 suppression by SB202190 only reversed the decrease in Bcl-2 expression. Inhibition of NF-κB by BAY 11-7082 markedly upregulated Bax level and decreased Bcl-2 expression, and eventually increasing the proportions of neuronal apoptosis compared with that in ACR alone. These results suggested that JNK contributed to ACR-induced apoptosis, while NF-κB acted as a protective regulator in response to ACR-induced neuropathy. This study helps to offer a deeper insight into the mechanism of ACR-induced neuropathy., (© 2018 Wiley Periodicals, Inc.)

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination., (Copyright © 2018 John Wiley & Sons, Ltd.)

Endodontic therapy is a routinely practised clinical procedure with few reported complications but, as a bleaching agent, inadvertent spillage of sodium hypochlorite beyond the root canal system may result in extensive soft tissue or nerve damage, and even airway compromise. Although very rare, complications arising from hypochlorite extrusion beyond the root apex are described. NaOCl causes oxidation of protein and lipid membrane and causes necrosis, hemolysis and dermal ulcerations (2-4). Neurological complication are very rare. Paraesthesia and anaesthesia may affect the mental, inferior dental and infra-orbital branches of the trigeminal nerve and normal sensation may take many months to  completely resolve (6, 7). Nerve damage (the buccal branch) was described in 2005 by Witton et al. (8) and patients exhibited a loss of the naso-labial groove and a down turning of the angle of the mouth and the motor function was regained after several months. We present a case in which the extrusion of NaOCl solution during endodontic therapy led to important destructive effects on soft tissues and nerves. The arisen medico legal issues are discussed.

Background: Vincristine (VCR) induced peripheral neuropathy is a common complication in children with acute lymphoblastic leukemia (ALL)., Procedures: A retrospective data analysis over an interval of 10 years (2006-2016) of all children with ALL seen at Sultan Qaboos University Hospital was carried out. Electronic medical records of eligible patients were reviewed. Patients with clinical evidence of neuropathy and abnormal nerve conduction studies (NCSs) were included in the study., Results: Nineteen (nine females and 10 males) out of 103 pediatric patients developed VCR-related neuropathy, and their age ranged between 2.5 and 14 years. Symptoms started after 2-11 doses of VCR. All 19 patients had documented peripheral neuropathy on NCSs. The autonomic nervous system and cranial nerves affection was relatively common in our patients; two presented with bradycardia, two patients with unexplained tachycardia, and five had abdominal pain and constipation, complicated by typhlitis in two patients. One patient developed unilateral hearing loss. Two patients developed severe life-threatening cranial nerve involvement with bilateral ptosis and recurrent laryngeal nerve involvement presented as vocal cord paralysis, hoarseness of voice, frequent chocking, and aspiration episodes., Conclusions: Peripheral neuropathy was the commonest form of VCR-related neuropathy. Autonomic neuropathy was relatively common in our patients. Cranial neuropathy is a serious side effect of VCR that can be severe, involving multiple cranial nerves and needs prompt recognition and management. Concomitant administration of pyridoxine and pyridostigmine does not seem to protect against further neurological damage in some patients., (© 2017 Wiley Periodicals, Inc.)

The widespread use of bisphosphonates, especially in osteoporosis, has led to a greater number of reports of side effects. We describe for the first time a case of a 75-year-old female patient with a history of indolent sicca syndrome who developed multiple cranial neuropathies after zoledronic acid infusion. In this case, the elimination of the main causes of multiple cranial neuropathies, the chronology with zoledronic acid infusion, the absence of secondary complications of the Sjögren's syndrome, reported cases of similar peripheral nerve injuries with interferon infusions, the spontaneous remission of this multiple cranial neuropathy in parallel with the induced flu-like syndrome, argue for its iatrogenic origin, probably by a great release of inflammatory mediators in this particular background of primary Sjögren's syndrome.

There have been recent reports of sarcoid-like granulomatosis development following the administration of tumor necrosis factor (TNF) inhibitors. To date, only four cases of neurosarcoidosis have been reported in association with TNF inhibitors, two of which were attributed to etanercept. We present the first case of etanercept-induced neurosarcoidosis involving multiple cranial neuropathies, including the trigeminal, facial, and vestibulocochlear nerves, while also highlighting the differential diagnoses of multiple cranial neuropathies and the association of TNF inhibitors and neurosarcoidosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We report a patient who suffered consecutive cranial neuropathies where each event was immediately preceded by the use of oral PDE-5 inhibitors. A discussion of the etiology of the events including possible interaction with other medications is included., (© 2015 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 65, 2015, ISSN 0065-955X, E-ISSN 1553-4448.)

A 10-year-old child presented after accidental exposure of the left eye to a blue hair dye containing methylene blue. Mild ocular surface changes and a selective blue staining of the usually invisible corneal nerve fibre bundles were present. Corneal sensitivity was reduced. Despite copious lubrication a transient neurotrophic keratitis developed which did not resolve until corneal sensitivity became normal 2 weeks later. Association of mild chemical burns with neurotrophic keratitis is unusual but is of high clinical relevance as keratitis is a vision-threatening complication.

The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected non-invasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20 mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to evaluate the long-term survival and late toxicities of concurrent-adjuvant chemotherapy in patients with stage III through IVB nasopharyngeal carcinoma (NPC) from endemic regions of China., Methods: Patients with stage III to IVB NPC were assigned randomly to receive radiotherapy (RT) alone (the RT group) or RT plus concurrent adjuvant chemotherapy (the CRT group). CRT patients received concurrent cisplatin (40 mg/m2) weekly during RT followed by cisplatin (80 mg/m2) and fluorouracil (800 mg/m(2) daily for 5 days) every 4 weeks for 3 cycles. The primary endpoint was overall survival., Results: In total, 316 patients underwent randomization, with 158 to each group. At a median follow-up of 70 months, the 5-year overall survival rate was 72% for the CRT group and 62% for the RT group (hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P = .043). Failure-free survival was significantly higher in the CRT group (P = .020). Most late toxicities were similar (33% vs. 26%; P = .089), except for cranial neuropathy (P = .042), peripheral neuropathy (P = .041), and ear damage (P = .048), which were significantly increased in the CRT group., Conclusions: The addition of concurrent adjuvant chemotherapy to RT provides survival benefits to patients with stage III through IVB NPC in endemic regions of China, and it does not increase most late toxicities apart from cranial neuropathy, peripheral neuropathy, and ear damage., (Copyright © 2013 American Cancer Society.)

Purpose: We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin., Methods: Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested., Results: Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63., Conclusions: In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency.

All-trans retinoic acid (ATRA) induces complete remission in 64-100 % of patients with acute promyelocytic leukemia (APL), and is considered to be a safe agent. Pseudotumor cerebri is a neurological side effect of ATRA reported in pediatric patients, and which is characterized by raised cerebrospinal fluid pressure in the absence of any intracranial pathology or secondary causes of intracranial hypertension. Involvement of cranial nerves other than II and VI is very uncommon in idiopathic intracranial hypertension (IIH); peripheral facial nerve palsy is exceptional and has rarely been described in the context of treatment with ATRA. We describe the case of a 15-year-old female patient with APL who developed an IIH and involvement of cranial nerves (bilateral papilledema, left facial and right sixth nerves) after receiving induction therapy including ATRA. Viral infections and other causes of secondary cranial nerve lesions were excluded. Symptoms completely subsided with the temporary withdrawal of ATRA and did not recur after reintroducing the drug. To date, the patient has managed to receive the treatment as per protocol. In conclusion, we report an atypical presentation of IIH that merits consideration, especially with respect to young patients with APL receiving ATRA; our most important observation is that the drug could be safely reintroduced once the symptoms had resolved.

Neuropathy is a well known side effect of vincristine, however cranial nerve toxicities are reported less frequently which can involve any cranial nerve in mostly bilateral pattern. As many patients have primary tumors or metastatic lesions in sites that could cause the clinician to overlook this reversible cause of neurologic dysfunction, the potential for misdiagnosis is high. Here, along with review of literature we describe three cases on vincristine who developed cranial neuropathy while on treatment.

Background: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination., Methods: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined., Results: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%)., Conclusion: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We present the case of a 24-year-old-female patient, who made an attempt to autolysis with valproic acid, benzodiazepines and neuroleptic. The valproic acid plasma level was very high (1437 μg/mL), confirming it was a severe intoxication. She presents an acute encephalopathy with prolonged status epilepticus, a lactic metabolic acidosis and hematologic disorders such as bicytopenia. Treatment including L-carnintine and continuous veno-venous haemodialysis (CVVHD) was rapidly introduced to prevent the occurrence of cerebral oedema. The evolution was favourable despite the occurrence of a nosocomial ventilation acute lung injury. The patient had motor sequelae of cranial nerves following status epilepticus extended, which disappeared spontaneously after several days., (2011 Elsevier Masson SAS. All rights reserved.)

CONTEXT. Although neurological toxicity from elemental mercury vapor and organic mercury exposure has been commonly reported in the literature, it is rarely reported from soft tissue injection of elemental mercury. We present a case of neurological dysfunction from subcutaneous injection of elemental mercury. CASE DETAILS. A 35-year-old Latin American man subacutely developed gait ataxia, diplopia, and vomiting 1 year after subcutaneous injection of elemental mercury, a practice common in Afro-Caribbean and Latin-American cultures. Physical examination showed an indurated plaque on his right shoulder at the injection site, left third nerve and bilateral sixth nerve palsies, nystagmus, dysarthria, and gait and limb ataxia. The patient's serum and 24-h urine mercury levels were significantly elevated; he underwent excision of the mercury reservoir and chelation with dimercaptosuccinic acid but experienced only mild improvement after 1 year. DISCUSSION. Neurological sequelae from elemental mercury, specifically cognitive dysfunction, tremor, cortical myoclonus, and peripheral neuropathy, have been reported but cranial neuropathies, ataxia, cerebrospinal fluid pleocytosis, and the presence of anti-Purkinje cell type-Tr antibody have not. Treatment involves removal of any existing mercury reservoir and chelation; however, improvement in neurological dysfunction after treatment has rarely been reported in the literature.

Root canal treatment is performed routinely in dental practice, using sodium hypochlorite which serves as an effective irrigant. The literature reviewed shows that several complications following irrigation with sodium hypochlorite may occur, but few practitioners are aware of it and its management. Such complications include injury to skin, oral mucosa and eyes, damage to clothing, air emphysema, allergic reactions, and injection beyond the foramen. In this article, a case report of injection with sodium hypochlorite beyond the foramen is presented, together with a review of the recent literature regarding common manifestations and case histories. The literature shows no standard management of this condition, but symptomatic therapies are discussed. It is important to minimize the risk of sodium-hypochlorite-induced damage during root canal therapy by use of protective measures, appropriate instrumentation and techniques, and consider alternate irrigation solutions.

Background: Transient, isolated lingual nerve neuropraxia is a rare complication following general anaesthesia. Reports implicate airway manipulation and we describe two new cases associated with laryngeal mask airway (LMA) and review the related English language literature., Results: Unilateral numbness and loss of taste on the anterior tongue were the characteristic symptoms. Collation of literature data (median and range) with that from the new cases showed: patient age was 38 (20-61) years and female to male ratio was 1.2:1. Surgery time was 62.5 (20-150) min and symptom duration was 28 (7-120) days., Conclusion: Lingual neuropraxias reported have been transient and patients can be advised, despite disturbing symptoms, that recovery is anticipated in about 1 month. Lingual neuropraxia reports are becoming more frequent, perhaps associated with increasing LMA use. Research is recommended as modification to LMA cuff volume, pressure and/or position within the oral cavity might ameliorate the entity.

Many authors described the effects on the fetus of maternal cocaine abuse during pregnancy. Vasoconstriction appears to be the common mechanism of action leading to a wide range of fetal anomalies. We report on an infant with multiple cranial-nerve involvement attributable to brainstem dysgenesis, born to a cocaine-addicted mother., (Copyright 2010 Elsevier Inc. All rights reserved.)

OraVerse, an injectable formulation of phentolamine mesylate (PM), was recently approved by the U.S. Food and Drug Administration (FDA) for reversal of anesthesia of the lip and tongue and associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. Because PM had not been approved previously for submucosal administration, 2 Good Laboratory Practices (GLP) studies in dogs designed to investigate systemic toxicity and the local effects of single and repeated dosing of OraVerse on the inferior alveolar nerve and branches of the superior alveolar nerve and adjacent soft tissues after local administration were conducted. Systemic toxicity was measured by preinjection and postinjection clinical examinations, clinical chemistry, and gross and microscopic examinations of major organs after necropsy. No evidence of systemic toxicity was detected. Local nerve and adjacent tissue damage was assessed by conventional histopathology. Nerve degeneration was evident in 1 animal. Mild perineural inflammation adjacent to the inferior alveolar nerve and inflammatory exudates were observed in submucosal tissues in several animals. No changes were observed in the nerves at injection sites of dogs from any dose group that were considered directly related to the test articles. These data reveal that single and repeated intraoral administrations of OraVerse are well tolerated in beagle dogs.

Purpose: To reveal the influence of retrobulbar capsaicin treatment on rats' eyes and to test the protective effects of PEDF, a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis., Methods: A single retrobulbar injection of capsaicin (50 mg/kg) was performed in young rats, and the effect of subsequent retrobulbar injections of PEDF 3.2 or 6.4 microg was recorded. Tear fluid alterations were evaluated with the Schirmer test and corneal alterations with slit lamp biomicroscopy. Histopathologic alterations were studied with light and electron microscopy. The number of leukocytes (myeloid cells) in the anterior and posterior chambers, peripheral retina, and vitreous were quantitatively evaluated., Results: Reduced tear secretion was found in capsaicin-treated rats compared with the control, but this effect was significantly attenuated by PEDF. Corneal ulceration developed and was followed by scar formation and neovascularization in the capsaicin-treated, and it was also significantly attenuated by PEDF treatment. Leukocyte infiltration of the anterior and posterior chambers, as well as the peripheral retina and vitreous, was also observed in capsaicin-treated eyes and was significantly reduced by PEDF treatment. The protective effects of PEDF were dose dependent for each parameter, even if the treatment was initiated at day 14 after the challenge., Conclusions: PEDF accelerated the recovery of tear secretion and also prevented capsaicin-induced neurotrophic keratouveitis and peripheral vitreoretinal inflammation. These effects of PEDF, described herein for the first time, may have a clinical application in inflammatory and neovascular diseases of the eye.

Using a new sequential analytic method, the safety of tetanus-diphtheria-acellular pertussis (Tdap) vaccine was monitored weekly among subjects aged 10-64 years during 2005-2008. Encephalopathy-encephalitis-meningitis, paralytic syndromes, seizures, cranial nerve disorders, and Guillain-Barré syndrome were selected as outcomes based on previous reports and biologic plausibility. The risk following Tdap was not significantly higher than the risk after Td. Statistical power was sufficient to detect a relative risk of 4-5 for Guillain-Barré syndrome and 1.5-2 for the other outcomes. This study provides reassurance that Tdap is similar in safety to Td regarding the outcomes studied and supports the viability of sequential analysis for post-licensure vaccine safety monitoring.

Objectives/hypothesis: Little is known regarding the phonatory consequences of unilateral external superior laryngeal nerve (ESLN) paralysis. By selectively blocking the ESLN with lidocaine HCl (with laryngeal electromyography verification), we modeled acute, unilateral cricothyroid (CT) muscle dysfunction to explore possible acoustic, aerodynamic, auditory-perceptual and auto-perceptive effects., Study Design: Prospective, repeated measures, experimental design., Methods: Ten, vocally-normal adult males underwent lidocaine block of the right ESLN. Multiple measures of phonatory function across a variety of vocal tasks/conditions were acquired before and during the block using standard data acquisition and analysis protocols., Results: During ESLN block, phonatory frequency range was significantly reduced with compression of both upper and lowermost regions of the pitch range. Mean speaking fundamental frequency increased significantly during oral reading. Acoustic analysis, aerodynamic assessment, and auditory- perceptual evaluation by blinded listeners revealed modest increases in phonatory instability (jitter), increased laryngeal airway resistance with no objective evidence of glottic insufficiency, and mild deterioration in voice quality most evident during high pitched voice productions, respectively. Participants uniformly rated their speaking and singing voices as worse during the block with significant weakness, effort, and tightness that they perceived as a mild level of impairment., Conclusions: These data support generally mild changes to the speaking voice, which extend beyond reductions in pitch range only, and shed light on the potential untoward phonatory effects of acute, unilateral CT dysfunction.

Background: In an RCT of PDT in the treatment of malignant gliomas, 3 patients developed cranial neuropathies after photoillumination. We are aware of no previous reports on cranial neuropathy after intracranial PDT., Methods: In a cohort of 80 patients, there were 41 men and 39 women; 47 were newly diagnosed and 33 had recurrent tumors. All patients underwent surgical tumor extirpation. There were 77 malignant gliomas, 2 meningiomas, and 1 metastatic tumor. The tumor locations were as follows: 39 frontal, 25 temporal, 12 parietal, and 4 occipital. Of the 25 patients with temporal lobe tumors, 18 received PDT., Results: Three of the 18 patients with temporal lobe tumors developed cranial neuropathies after PDT. The floor of the middle fossa received photoillumination in all 3 patients. This complication was not seen in any other patient with tumors in the frontal, parietal, or occipital regions, or patients with temporal lobe tumors who did not receive PDT. The first patient developed seventh nerve paresis and hypoesthesia in fifth nerve distribution, which resolved only partially. The second patient developed a seventh nerve paresis that resolved completely. The third patient developed transient neuralgic pain in the trigeminal nerve distribution., Conclusions: Cranial neuropathies could be the result of photoillumination of fifth and seventh cranial nerves during PDT of the temporal fossa. We recommend shielding of the middle fossa floor during PDT.

Vincristine is a commonly used antineoplastic drug and frequently causes neurotoxicity. Here the authors report a 4-year-old boy with acute lymphoblastic leukemia in whom vincristine-induced peripheral and cranial neuropathy developed during remission induction therapy. The patient seemed to benefit from pyridoxine and pyridostigmine therapy greatly and this therapy is recommended in patients with severe vincristine-induced neuropathy.

We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

Introduction: Leflunomide is a new drug for the treatment of rheumatoid arthritis. Its mechanism of action is based on lymphocyte inhibition. We report the cases of two patients treated with leflunomide who developed severe sensory-motor axonal polyneuropathy., Observation: Two women (61- and 70-year-old) presented with a sensory-motor axonal polyneuropathy beginning 5 months after onset of leflunomide treatment. Etiologic investigations were negative. The symptoms rapidly improved after withdrawing leflunomide., Discussion: The analysis of drug watch data found twelve patients with leflunomide-related neuropathy. Ten of them were more than 60 years old. The mean delay for onset of neuropathy was 9 months. The neuropathy improved after treatment withdrawal in seven patients., Conclusion: We consider these data strongly suggest that leflunomide is a cause of axonal sensory-motor neuropathy. The prevalence of such adverse events is still unknown.

Previous studies have demonstrated that adult rats with excitotoxic lesions of the hippocampus display deficits in memory-related behaviors similar to the memory deficits associated with schizophrenia. In this study, we assessed the sub-chronic effects of quetiapine, risperidone and haloperidol on performance deficits after intracerebroventricular administration of the excitotoxin, kainic acid, using paradigms for contextual and cued fear conditioning and spatial reversal learning in rats. The effects of three doses of quetiapine (5, 10 and 20 mg/kg) and single doses of risperidone (0.5 mg/kg) and haloperidol (0.15 mg/kg) were compared. Quetiapine administration at the lowest dose (5 mg/kg) reversed deficits in contextual and cued fear conditioning, but not deficits in spatial reversal learning, in kainic acid-treated animals. However, the two higher doses of quetiapine, and the single doses of risperidone and haloperidol, did not reverse any of the kainic acid-induced behavioral deficits. These results may be relevant to the effects of quetiapine and other antipsychotic drugs on memory deficits in patients with schizophrenia.

The authors reviewed the histories of 33 patients (ages 44 to 50 years) treated with IV thrombolysis for acute stroke due to spontaneous cervical carotid artery dissection. Median NIH Stroke Scale (NIHSS) score on admission was 15. No new or worsened local signs, subarachnoid hemorrhage, pseudoaneurysm formation, or rupture of the cervical ICA were observed. At 3 months, median NIHSS was 7 and median modified Rankin Scale (mRS) 2.5; mRS < or = 2 was observed in 17 patients.

The authors report a 24-year-old man who developed encephalopathy and rapid quadriplegia following ingestion of a solution containing diethylene glycol (DEG). As quadriparesis evolved, motor response amplitudes were markedly reduced with preserved conduction velocities. Studies during clinical recovery revealed marked motor conduction velocity slowing and prolonged distal latencies. These data indicate that DEG intoxication may cause a primary acute axonal sensorimotor polyneuropathy with demyelinating physiology during recovery.

Cranial multineuropathy is an uncommon occurrence. We observed two cases of multinevritis of the cranial nerves which had many features in common: acute onset after toxic inhalation, occurrence of neuroparaxic block, and rapid resolution after corticosteroid therapy. We believe physicians should be aware that multinevritis of the cranial nerves may be related to acute exposure to toxic substances. Missing this diagnosis could lead to a delay in therapy.

Adverse effects of acute exposure to hydrogen sulfide (H2S) are well documented, but long-term effects of occupational exposure to low levels of the gas are not. To evaluate effects of such exposure we performed physical, neurologic, psychiatric, and chemosensory (smell and taste) examinations of four workers who were present but did not lose consciousness when the gas was accidentally released at a construction site. None of the four workers tested positive for functional problems, but all met diagnostic criteria for at least three, and up to eight, H2S-induced neuropsychiatric clinical disorders and from zero to two subclinical disorders. All four had abnormal P300 evoked responses (electrical neurophysiologic tests of brain waves). Our data indicate that exposures to even relatively low concentrations of H2S are hazardous. A rigorous epidemiologic investigation of persons who work with H2S is warranted.

The cyclic somatostatin analog, octreotide, forms the mainstay of medical treatment for acromegaly. In addition to lowering circulating growth hormone levels and shrinking tumor size, octreotide may provide symptomatic relief of headaches associated with growth hormone secreting tumors. The majority of reported complications of octreotide therapy are gastrointestinal and metabolic. The present case illustrates the development of acute bilateral cavernous sinus syndrome with loss of eye movement bilaterally during octreotide therapy. Serial MRI examination suggest tumor infarction as the etiology. The symptoms resolved over 2 months as the tumor shrunk in size and growth hormone was dramatically reduced.

A lesion of the IAN following endodontic treatment of the lower molars and premolars is not a rare event and presents an uncomfortable situation both for the dental surgeon and the patient. Injury can result on the one hand by direct intrusion of the instrument through the apex into the mandibular canal, and on the other by the filling material which becomes forced into the mandibular canal. In the latter case, a nerve lesion will only result when the filling material contains neurotoxic substances such as paraformaldehyde. With a direct lesion or when forcing of resorbable filling material into the mandibular canal is suspected, one should first employ a wait-and-see approach, because usually the only nerve damage is in the form of neuropraxy or axonotmesis for which there is a high rate of spontaneous regeneration. However, if neurotoxic filling material is introduced into the direct vicinity of the nerves, the mandibular canal should be opened and the filling material should be removed as early as possible. If the filling material is forced directly within the endoneurium between the nerve bundles, the damaged nerve sections must be resected and bridged using transplants from the sural or greater auricular nerves.