Case of tizanidine withdrawal showing hallucination, decorticate posture and tremor, with hypersympathetic vital signs.

Tizanidine, an α2-adrenergic receptor agonist commonly prescribed as a muscle relaxant, has been associated with limited cases of acute intoxication or withdrawal. Here, we present a case of tizanidine withdrawal in a woman in her 40s who presented with an unusual combination of systemic and neurological symptoms. These included hallucinations, decorticate posture, limb and eyelid tremors, along with hypertension, tachycardia and tachypnoea. The diagnosis of tizanidine withdrawal was established by a comprehensive assessment of the patient's medical history and the systematic exclusion of other potential diseases. Our approach to managing the withdrawal symptoms was to initiate symptomatic treatment with a combination of a beta-blocker and a calcium channel blocker. Remarkably, this intervention successfully resolved both vital signs and neurological manifestations by the following day. In conclusion, tizanidine withdrawal is associated with a distinct and diagnostically significant neurological syndrome characterised by hallucinations, decorticate posture, tremors and hypersympathetic vital signs.

Ertapenem-induced encephalopathy in a patient with liver abscess and acute kidney injury.

A man in his late 70s, retired and independent, generally fit and well with a history of normal cognitive function baseline presented with liver abscess and acute kidney injury. He received meropenem 1 g three times a day for 15 days then subsequently changed to ertapenem 1 g one time a day in preparation for outpatient antibiotic treatment. After 2 days of starting ertapenem, the patient developed night-time delirium, decreased orientation and insomnia, loss of appetite, jerking and hallucination. Investigations have been done to investigate the cause of acute delirium, including lumbar puncture, CT brain, MRI brain, repeat CT abdomen and pelvis to monitor the liver abscess, and electroencephalogram but results were all unremarkable. Medication history during admission was reviewed and discontinued one by one the medications that were suspected to have caused the encephalopathy. Two days following the discontinuation of ertapenem, the patient's symptoms improved with a rapid return to his baseline and without neurological deficit.

Toxic optic neuropathy associated with lamotrigine and levetiracetam dual therapy.

We report the case of an early adolescent male on lamotrigine and levetiracetam therapy with a 1-month history of progressive, bilateral, painless visual loss which resolved on cessation of lamotrigine. To our knowledge, we present the first case of lamotrigine and levetiracetam dual therapy associated with toxic optic neuropathy, supported by electrophysiology and optical coherence tomography (OCT) changes. Electrophysiology findings were consistent with retinal ganglion cell dysfunction, with bilateral optic nerve involvement. Macula OCT showed mild retinal ganglion cell loss in all inner quadrants bilaterally. This case highlights the importance of asking patients with epilepsy treated with lamotrigine and levetiracetam about visual problems and considering early dose reduction or cessation of treatment.

Posterior reversible encephalopathy syndrome (PRES) in classic Hodgkin's lymphoma, complicated by anthracycline-induced cardiomyopathy.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.

Hyperammonemic encephalopathy induced by valproic acid.

Valproate (VPA) is broad-spectrum antiepileptic drug. Several adverse reactions including hepatotoxicity, fetal risk and pancreatitis are well known and labelled as boxed warnings in the USA. One adverse reaction that is less well known but clinically significant for its severe morbidity is hyperammonemic encephalopathy. We present a case of woman with hyperammonemic encephalopathy following the initiation of VPA therapy; she had a favourable outcome with discontinuation of the drug and prompt treatment with lactulose and L-carnitine.

Valproate overdose leading to hyperammonaemic encephalopathy.

Sodium valproate is a commonly prescribed anticonvulsant medication; however, it can cause uncommon side effects such as hyperammonaemia and encephalopathy. We present the case of a male in his early 50s brought to the emergency department after being found collapsed by his wife, with an empty bottle of sodium valproate tablets. The patient developed hyperammonaemic encephalopathy due to sodium valproate overdose and was treated with supportive care and renal replacement therapy. This case highlights the importance of recognising the potential complications of sodium valproate and its prompt treatment.

Varicella-zoster virus vasculopathy in a patient with multiple sclerosis receiving natalizumab.

We present a case of a woman in her 30s with relapsing-remitting multiple sclerosis, treated with natalizumab, who developed ophthalmic varicella zoster virus (VZV) infection, with subsequent vasculopathy causing cerebral ischaemic lesions. She was treated with acyclovir, prednisolone and acetylsalicylic acid and fully recovered. VZV vasculopathy is associated with stroke and immunomodulating treatments may increase the risks of these adverse events. To date, nine VZV-related vasculopathy cases in patients treated with natalizumab have been reported in English literature and are summarised in this paper. Although rare, VZV intracerebral vasculopathy is an important differential diagnosis in patients with unexplained new-onset neurological symptoms after a herpes zoster infection. Treatment guidelines for VZV vasculopathy and for continuing treatment of multiple sclerosis after such an event are currently not established.

Progressive multifocal leukoencephalopathy associated with carbamazepine-induced immune dysfunction and recovery after carbamazepine cessation.

A patient with epilepsy on carbamazepine developed a rapidly progressive cerebellar syndrome. Serial MRI showed progressive posterior fossa T2/fluid attenuated inversion recovery hyperintensity with gadolinium enhancement. Standard cerebrospinal fluid (CSF) analysis was normal. Detection of John Cunningham virus DNA in the CSF confirmed progressive multifocal leukoencephalopathy (PML). The only evidence of immune disfunction was hypogammaglobulinaemia and longstanding lymphopenia. After cessation of carbamazepine, the lymphocyte count and immunoglobulin levels returned to normal and the PML resolved, with good clinical recovery. No specific treatments for PML were given. We hypothesise that PML in this case was due to carbamazepine-induced prolonged mild immunosuppression with reconstitution of the immune system after carbamazepine cessation, resulting in recovery from PML. Effects of anticonvulsants on immune function and infection risk may contribute to epilepsy-related morbidity and mortality. Further investigation is needed to determine the frequency of immune dysfunction and infections in patients treated with anticonvulsants such as carbamazepine and whether interventions could reduce infection risk.

Sixteen syndrome: a rare presentation of central demyelination.

This case illustrates two diagnostic challenges for clinicians: the rarely described sixteen syndrome and the relationship between tumour necrosis factor (TNF)-alpha inhibitors and central demyelination. Sixteen syndrome affects horizontal eye movements and the facial nerve bilaterally reflecting a lesion in the posterior pontine tegmentum, adjacent to the fourth ventricle. Given its rarity and complexity of clinical signs, this syndrome risks misdiagnosis and mismanagement. The relationship between TNF-alpha inhibitors and demyelination is a complex issue in which causality is yet to be established. This diagnostic challenge poses a management dilemma for clinicians.

Antiepileptic drug-induced severe granulomatous interstitial nephritis.

Granulomatous interstitial nephritis (GIN) is a type of tubulointerstitial nephritis characterised by tubulointerstitial infiltration of mononuclear cells and eosinophils. It accounts for about 6% of all tubulointerstitial nephritis and is detected in ∼0.5%-0.9% of all renal biopsies. GIN has been linked to several antibiotics, non steroidal anti-inflammatory drugs (NSAIDs), and granulomatous disorders like tuberculosis and sarcoidosis but is rarely reported with anti-epileptic medications like phenytoin and levetiracetam. We present a case report of a man in his early 20's with previously normal renal function who developed GIN following levetiracetam and phenytoin consumption for 7 years. After withdrawal of the causative drug and starting steroid therapy, his kidney function gradually improved. In cases of GIN, medication history is important in the evaluation of aetiology.

Cocaine-induced rhabdomyolysis and compartment syndrome.

A man in his 30s with a history of cocaine and intranasal heroin use presented to the emergency department with severe leg pain and weakness. Physical examination findings were significant for tachycardia, absence of dorsalis pedis pulses, tense and painful calf muscles along with absence of plantar reflexes in bilateral lower extremities. Laboratory investigations were significant for positive urinary drug screen for cocaine, severe rhabdomyolysis and acute kidney injury. Given the absence of dorsalis pedis pulses in bilateral lower extremities and radiological evidence of oedematous changes in calf muscles with perimuscular oedema, a diagnosis of compartment syndrome was made. He was treated with bilateral lower extremity four-compartment fasciotomies and haemodialysis for acute kidney injury. Rhabdomyolysis has been attributed to cocaine use; however, compartment syndrome is a very rare complication, especially in the absence of trauma or prolonged immobilisation.

Siponimod-related bilateral cystoid macular oedema and intravenous fluorescein angiographic findings in a patient with stable proliferative diabetic retinopathy without history of diabetic macular oedema.

Siponimod is a sphingosine-1-phosphate receptor modulator used as disease-modifying therapy for relapsing-remitting multiple sclerosis similar to Fingolimod which has been known to cause dose dependent fingolimod associated macular oedema (FAME). We report a case of delayed onset bilateral cystoid macular oedema in a patient with stable proliferative diabetic retinopathy who developed cystoid macular oedema in the setting of siponimod (Mayzent; Novartis Pharmaceuticals; Cambridge, Massachusetts, USA) use. As with FAME, cystoid macular oedema resolved in the patient's eyes with drug cessation and adjunctive topical anti-inflammatory therapy. We highlight unique fluorescein angiographic findings within this class of drugs as well as the clinical challenge posed by comorbid diabetic and inflammatory ophthalmic pathology.

Atypical presentation and diagnosis of AIDS-related CMV encephalitis.

We report a case of man in his 40s with a medical history of post-traumatic stress disorder who presented to the emergency department with altered mental status, ataxia, headache and dizziness a few hours after snorting amphetamines and mushrooms. Twenty-four hours after presentation, while no longer abusing amphetamines or mushrooms, he remained ataxic and dizzy. A CT scan of the head showed periventricular hypodensities. MRI of the brain revealed extensive confluent T2 hyperintense signal throughout the cerebral white matter, brainstem and cerebellar white matter. Given these findings and persistent ataxia, lumbar puncture was performed, and cerebrospinal fluid (CSF) meningoencephalitis panel was positive for cytomegalovirus (CMV), prompting a diagnosis of CMV encephalitis. Since CMV almost always occurs in the setting of immunocompromise, the patient was screened for HIV and found to be positive with a CD4 count of 22. He was treated with ganciclovir 5 mg/kg/dose intravenously every 12 hours, with resolution of all symptoms.

Response of focal refractory status epilepticus to lacosamide in an infant.

Status epilepticus (SE) is a life-threatening medical emergency which is frequently encountered in the critical care setting and can be refractory to treatment. Refractory status epilepticus (RSE) is defined as SE that has failed to respond to adequately used first-line and second-line antiepileptic medications. Super refractory status epilepticus is defined as SE that persists for 24 hours or more after the use of an anaesthetic agent or recurs after its withdrawal.If SE persists beyond a period of 7 days it is referred to as prolonged, refractory status epilepticus (PRSE). There are limited data guiding treatment of RSE in the paediatric population.Lacosamide (LCM) is licensed as an adjunctive treatment for partial-onset seizures. Evidence for the efficacy of LCM in paediatric SE is scarce. This case report may suggest a synergistic effect of LCM on slow-activation sodium channels in conjunction with medications such as phenytoin that causes fast inactivation of sodium channels. The dual fast and slow inactivation of sodium channels may enhance the effectiveness in treatment of RSE. This is the first case report of PRSE in an infant, successfully treated with LCM. A brief review of literature is also a part of this report.

Successful thrombolysis in essential thrombocythemia-related acute ischaemic stroke.

Essential thrombocythemia (ET)-related acute ischaemic stroke (AIS) may account for approximately 0.25%-0.5% of all ischaemic strokes. If left undiagnosed and untreated, patients with ET carry an increased risk of recurrent thrombosis involving major organs including the brain. We report an interesting case of a 67-year-old man, who was successfully thrombolysed for AIS resulting from ET. He presented with sudden onset of left-sided hemiparesis with a left-ventricular clot. His subsequent investigations including positive JAK2 V617F mutation confirmed the diagnosis of ET. He made a significant recovery with thrombolysis, anticoagulation, antiplatelet and hydroxyurea. A fear of post-thrombolytic haemorrhagic complications appears the major reason for the lack of reports of thrombolysis in ET-related AIS. Although the diagnosis of ET was confirmed on subsequent investigations, successful thrombolysis in our case provides preliminary evidence that ET-related AIS cases can undergo successful thrombolysis using tenecteplase. To date, ours is only the second case of ET-related AIS being thrombolysed.

Zonisamide as treatment option in persistent migraine aura.

Persistent migraine aura without infarction is a rare but debilitating condition. Treatment options are mostly anecdotal and limited due to inefficacy and side effects. We present a 16-year-old female patient with triple X syndrome, having persistent aura symptoms for over 2 years, consisting of continuous visual and sensory sensations. Previous treatments with seven different migraine preventatives were not successful. The patient successfully responded to zonisamide against refractory prolonged aura and remained symptom-free under the ongoing treatment without any relevant side effects. Zonisamide may be considered a new and safe treatment option for patients with persistent migraine aura.

Severe amnestic syndrome due to theophylline toxicity.

We report a case of severe amnestic syndrome following theophylline overdose. A woman in her early 30s was admitted to hospital where she developed status epilepticus following an intentional overdose of theophylline and lansoprazole. She developed a profound acidosis and required intubation in the intensive care unit. Following extubation the patient was noted to have a severe amnestic syndrome with poor short-term memory. A work-up to exclude infectious, autoimmune and paraneoplastic causes for encephalitis was undertaken. Cerebrospinal fluid analysis was normal and autoimmune encephalitis titres were negative. Initial MRI brain imaging demonstrated hyperintensities of the mesial temporal lobes bilaterally. Follow-up imaging at 4 months identified further interval reduction but persistent hippocampal hyperintensities. Theophylline toxicity with corresponding amnestic syndrome and hippocampal hyperintensities has been rarely reported. We believe this case with persistent abnormal Montreal Cognitive Assessment Score at 12 months correlates with persistent hippocampal abnormalities seen on imaging.

Metronidazole-induced reversible cerebellar dysfunction.

A 73-year-old man who presented with fever and abdominal discomfort was diagnosed to have a liver abscess. He was treated with antimicrobials which included metronidazole. One month into treatment, he developed neurological symptoms and signs that were suggestive of cerebellar pathology. MRI of the brain showed T2/fluid attenuated inversion recovery hyperintensities involving bilateral dentate, fastigial and interpositus nuclei. After excluding common aetiologies, the possibility of metronidazole-induced neurotoxicity was considered. After stopping metronidazole, his symptoms and signs resolved. A subsequent MRI scan of the brain showed reversal of changes. Neurotoxicity caused by metronidazole is an uncommon adverse effect of a commonly used antimicrobial drug and should be considered in the appropriate clinical scenario.

Management of refractory pain in Stiff-Person syndrome.

Stiff-Person syndrome (SPS) is a rare autoimmune neurological disorder characterised by episodic painful muscle rigidity and violent spasms. A significant trigger for the painful spasms experienced by patients is pain itself, making optimal pain management and avoidance a necessity. While first-line and second-line therapies for spasm prevention and termination are known, there is a paucity of evidence to guide pain management. We report the case of a 26-year-old woman with SPS referred for excruciating muscle cramping and rigidity with pain lasting beyond the episodes themselves. We report the novel use of ketamine and intravenous magnesium sulfate which may provide analgesia, spasm avoidance and early termination of exacerbations in SPS.

Older-onset levodopa-responsive parkinsonism with normal DAT-SPECT and pterin hypometabolism.

Pterin species participate in dopamine biosynthesis, and abnormal pteridine metabolism contributes to reduced dopamine. GTP cyclohydrolase 1 (GCH-1) deficiency, which triggers pteridine hypometabolism and normally develops in childhood, can mediate an adult-onset decrease in levodopa production and dopa-responsive dystonia (DRD), with normal dopamine transporter single-photon emission computed tomography (DAT-SPECT). A recent study described normal DAT-SPECT in adult-onset cases with GCH-1 mutations, clinically diagnosed with Parkinson's disease, which raises the possibility that the abnormal metabolism of pteridine may be a differential diagnosis for adult-onset parkinsonism. We report an older patient with levodopa-responsive parkinsonism with normal DAT-SPECT, or scans without evidence of dopamine deficit (SWEDD), whose biochemical analysis showed pterin hypometabolism, which occurs in GCH-1-deficient DRD. Surprisingly, this patient presented no dystonia or GCH-1 gene mutation or deletion. This case suggests that low pterin metabolism should be considered in older-onset levodopa-responsive parkinsonism with normal DAT-SPECT, even without GCH-1 mutations or deletions.