Cranial Nerve Disorders Associated With Immune Checkpoint Inhibitors.

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.

Ethylene glycol intoxication following brake fluid ingestion complicated with unilateral facial nerve palsy: a case report.

BACKGROUND: Brake oil is an automobile transmission fluid composed of a mixture of toxic alcohols such as ethylene glycols and glycol ethers. Both accidental and intentional ingestion cases have been reported and they can present with multisystem involvement. Life-threatening complications evolve from deleterious effects on cardiopulmonary and renal systems. Effects on neurological and gastrointestinal systems give rise to a multitude of complications although non-fatal in nature. The biochemical panel consists of a high concentration of ethylene glycol with severe metabolic acidosis, high anion gap, high osmolar gap, oxaluria, and hypocalcemia. The mainstay of treatment is enhanced elimination of ethylene glycol and its metabolites by hemodialysis, together with general supportive care, gastric decontamination, and vitamins such as thiamine and pyridoxine to minimize the adverse effects of intoxication. CASE PRESENTATION: A 26-year-old Sinhalese woman presented with reduced urine output, shortness of breath, reduced level of consciousness, abdominal pain, and vomiting with mild degree fever of 2 days' duration. She had bilateral lower limb edema, crepitations over bilateral lower lung fields, and right-sided lower motor type facial nerve palsy. Investigations showed severe metabolic acidosis with high anion gap and high osmolar gap. With regular hemodialysis she made a complete recovery after 3 months. CONCLUSION: Even without a clear history of poisoning, the presence of a high anion, high osmolar gap metabolic acidosis should prompt one to search for ethylene glycol ingestion. Uncommon manifestations like cranial neuropathies need to be examined and considered. Timely aggressive treatment leads to a better prognosis.

Facial nerve palsy and laryngospasm as a complication of local anaesthesia during adenotonsillectomy.

Tonsil surgeries are the most frequently performed surgical procedures in ENT departments. We would like to present the case of a 5-year-old patient who suffered from unilateral peripheral facial nerve palsy and laryngeal spasm following adenotonsillectomy. Paresis was observed immediately after the transfer of the patient to the postoperative room. The activity of facial muscles was restored within 2 hours from the beginning of the surgery. We assume that this was the direct effect of an anaesthetic on the extracranial processes of the facial nerve.

Differential Development of Facial and Hind Paw Allodynia in a Nitroglycerin-Induced Mouse Model of Chronic Migraine: Role of Capsaicin Sensitive Primary Afferents.

Despite the relatively high prevalence of migraine or headache, the pathophysiological mechanisms triggering headache-associated peripheral hypersensitivities, are unknown. Since nitric oxide (NO) is well known as a causative factor in the pathogenesis of migraine or migraine-associated hypersensitivities, a mouse model has been established using systemic administration of the NO donor, nitroglycerin (NTG). Here we tried to investigate the time course development of facial or hindpaw hypersensitivity after repetitive NTG injection. NTG (10 mg/kg) was administrated to mice every other day for nine days. Two hours post-injection, NTG produced acute mechanical and heat hypersensitivity in the hind paws. By contrast, cold allodynia, but not mechanical hypersensitivity, occurred in the facial region. Moreover, this hindpaws mechanical hypersensitivity and the facial cold allodynia was progressive and long-lasting. We subsequently examined whether the depletion of capsaicin-sensitive primary afferents (CSPAs) with resiniferatoxin (RTX, 0.02 mg/kg) altered these peripheral hypersensitivities in NTG-treated mice. RTX pretreatment did not affect the NTG-induced mechanical allodynia in the hind paws nor the cold allodynia in the facial region, but it did inhibit the development of hind paw heat hyperalgesia. Similarly, NTG injection produced significant hindpaw mechanical allodynia or facial cold allodynia, but not heat hyperalgesia in transient receptor potential type V1 (TRPV1) knockout mice. These findings demonstrate that different peripheral hypersensitivities develop in the face versus hindpaw regions in a mouse model of repetitive NTG-induced migraine, and that these hindpaw mechanical hypersensitivity and facial cold allodynia are not mediated by the activation of CSPAs.

Cranial neuropathies after intracranial Photofrin-photodynamic therapy for malignant supratentorial gliomas-a report on 3 cases.

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.

Facial motion analysis of acid burn victims--development of a new facial motion impairment index.

OBJECTIVES: Evaluation of facial movement is necessary for the assessment of motor deficits and planning reconstructive surgery in facial burns. Clinicians recognise the need for an accurate and reproducible method of functional assessment. We propose a new facial functional impairment index (FFII) for assessing facial motor dysfunction due to severe burn injury and provide inter/intra-patient comparison for documenting rehabilitation. METHODS: The maximal static response assay (MSRA) was used to compare facial movement in 20 acid burn victims with 20 control subjects. Data compiled from 12 soft tissue landmarks was used to quantify rest and dynamic asymmetry, anatomic and non-anatomic motion and calculate the FMII. The Katz score, Nottingham index and number of affected aesthetic units provided insight into FFII efficacy. RESULTS: Patients with greater aesthetic disfigurement demonstrated significantly poorer anatomic function (c=0.62; p=0.03) as well as larger global facial functional impairment (c=0.52; p=0.08). CONCLUSION: Acid burns caused severe asymmetry and functional impairment. The FFII is a composite score of global function based on a reproducible method of data collection and it differentiated between acid burn victims and provided objective comparative measures. Software automation, integration of video and 3D data, appropriate graphical and pictorial depiction of variables and measurements, and further research into the accuracy of FFII as a marker of clinical recovery and assessment of function in facial burns, will enhance future clinical applications and potentially aid surgical reconstruction.

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.

Facial nerve palsy after acute exposure to dichloromethane.

BACKGROUND: Dichloromethane poisoning affects predominantly the central nervous and the cardiovascular systems, and results from both carboxyhemoglobin formation and direct solvent-related narcosis. Exposure is frequently occupational and related to paint-stripping. Several reports have described severe adverse effects as well as fatalities. Conflicting reports regarding peripheral nerve toxicity have been found with no reports of clinical acute toxicity heretofore. METHODS: We present a case report of a patient who developed a facial nerve palsy after acute occupational exposure to Dichloromethane. The patient was part of a paint removing crew who have worked without proper protecting measures and were thus exposed to high levels of Dichoromethane. RESULTS: The patient was involved in paint stripping with Dichloromethane, and developed facial nerve palsy. Other known causes of facial palsy were excluded, and although idiopathic palsy cannot be ruled out, there were no corroborating findings. Carboxyhemoglobin levels taken after a significant delay were normal. CONCLUSION: This is the first article that describes a case of Facial Nerve Palsy related to acute dichloromethane exposure, indicating a possible peripheral neurotoxic effect of this solvent.

Neurological complications following extrusion of sodium hypochlorite solution during root canal treatment.

AIM: To report the presentation and management of two cases with neurological complications secondary to the extrusion of sodium hypochlorite solution into the facial soft tissues during root canal treatment. SUMMARY: The clinical features, with particular emphasis on nerve deficit following inadvertent extrusion of sodium hypochlorite, are discussed and its management highlighted. Early and aggressive treatment is advocated following such incidents in order to reduce potentially serious complications. KEY LEARNING POINTS: *Neurological sequelae can follow inadvertent hypochlorite extrusion. *Early recognition may avert a potentially more serious outcome. *Active hospital treatment including intravenous steroids and antibiotics is recommended.

Delayed facial nerve paresis following acoustic neuroma resection and postoperative vasoactive treatment.

OBJECT: Delayed facial nerve paresis is a well known clinical phenomenon following acoustic neuroma surgery, typically occurring early during the postoperative course. The clinical course of the delayed facial nerve paresis and intraoperative electromyographic (EMG) signals were evaluated in a subgroup of patients who underwent vasoactive treatment for preservation of hearing and developed secondary deterioration after termination of treatment. METHODS: Between 1990 and 2001 seven patients were identified who received vasoactive treatment for preservation of hearing and developed a delayed facial nerve paresis after termination of medication. Intraoperative facial nerve EMG activity was analyzed in six patients. RESULTS: All patients developed a delayed facial nerve paresis between 2-5 days following termination of a 10 day treatment consisting of HES and nimodipine. Medication was re-initiated and the facial nerve paresis improved in all patients. In two patients intraoperative EMG signals revealed "A-trains" waveform patterns, which are highly suggestive for an immediate postoperative facial nerve paresis, whereas in four patients no pathognomonic EMG patterns could be recorded. CONCLUSIONS: The delayed onset of a facial paresis following termination of vasoactive treatment points to a disturbed microcirculation of the nerve as the main pathophysiological feature. Two groups could be identified on the basis of intraoperative EMG activity. In one group with presence of "A-trains" medication apparently masked the onset of an immediate postoperative facial nerve deficit. Four patients without "A-trains" did not develop a typical delayed facial nerve paresis during vasoactive treatment, but thereafter. The time lag between termination of treatment and onset of a delayed palsy points to a protective effect due to improved microcirculation.

Facial nerve palsy after intracisternal papaverine application during aneurysm surgery--case report.

A 61-year-old woman suffered transient mydriasis and prolonged facial nerve palsy after intracisternal papaverine application subsequent to elective clipping of an unruptured middle cerebral artery aneurysm. The mydriasis resolved within 90 minutes, but the facial nerve dysfunction persisted for 2 months before complete recovery. Prolonged irrigation of the cisterns may have washed the papaverine into contact with the facial nerve. This case supports previously reported evidence of a possible effect of topical intracisternal papaverine hydrochloride application on the facial nerve.

Absolute ethanol embolization for peripheral arteriovenous malformation: report of two cures.

We have reported two patients in whom absolute ethanol was used to sclerose arteriovenous malformations. Because of its low viscosity, liquid form, and devastating effect when injected intra-arterially, absolute ethanol is effective in treating AVMs, and it has been proven to have curative potential. For these same reasons it is also potentially harmful, particularly to nerves and possibly to skin.