Encephalopathy and Encephalitis Flashcards
Limbic Encephalitis
Limbic encephalitis represents a group of autoimmune conditions characterised by inflammation of the limbic system and other parts of the brain. People with limbic encephalitis typically presents with a subacute development of memory impairment, confusion, and alteration of consciousness, often accompanied by seizures and temporal lobe signal change on MRI.
It is important to diagnose the underlying autoimmune aetiology of limbic encephalitis as this might point you toward the underlying diagnosis of cancer. This is to say that limbic encephalitis may often present as a paraneoplastic syndrome, although not always. The antibodies that cause limbic encephalitis and their associated malignancies are:
NMDA receptor antibodies = ovarian cancer
Voltage-gated potassium channel antibodies = Thymoma or small cell lung cancer
Anti-Hu antibodies = Small cell lung cancer
Anti-GAD = Thymoma
anti-Ma2 antibodies = Germ-cell tumours of testis, non-small cell lung cancer
Example Question:
A 45-year-old lady has had weight loss over the last eight months. Over the last 3 months, she has become confused according to her family, forgetting things she would normally remember like telephone numbers or what she did during the day. She has now presented with a second episode of what sounds like a generalised tonic-clonic seizure in the last week. She has no other past medical history of note. Clinical examination shows MMSE of 23/30, cachexia, a bulky left adnexal region, and nil else. Routine blood tests are unremarkable. You organise a CT chest, abdomen, pelvis and head which reveal a suspicious lesion in the left ovary but are otherwise normal. You organise a biopsy of the left ovary, send off a paraneoplastic blood screen, and order an MRI of the brain. What would you expect the paraneoplastic screen to return showing?
Voltage-gated potassium channel antibodies Anti-Hu antibodies Anti-GAD Anti-Ma2 antibodies > NMDA receptor antibodies
Autoimmune Encephalitis - Types
Types of autoimmune encephalitis include:
- autoimmune limbic encephalitis (paraneoplastic and non-paraneoplastic)
- Rasmussen’s encephalitis
- anti-NMDAR (NR1) encephalitis
- glycine-receptor mediated encephalitis
- Bickerstaff brainstem encephalitis
Posterior Reversible Leucoencephalopathy (PRES)
Posterior reversible leucoencephalopathy syndrome may present with thunderclap headache, usually followed rapidly by confusion, seizures and visual symptoms. CT brain and lumbar puncture results are usually normal or near normal. The most common causes of PRES are hypertensive encephalopathy and eclampsia. Hypertension is commonly observed. Diagnosis is made by evidence of vasogenic brain oedema on MRI brain. PRES is often associated with reversible cerebrovascular vasoconstriction syndrome with vasospasms on angiography. Acute disseminated encephalomyelitis does not present with thunderclap headache.
Wernicke’s Encephalopathy
Wernicke’s encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke’s encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls
Features nystagmus (the most common ocular sign) ophthalmoplegia ataxia confusion, altered GCS peripheral sensory neuropathy
Investigations
decreased red cell transketolase
MRI
Treatment is with urgent replacement of thiamine
Relationship with Korsakoff syndrome
If not treated Korsakoff’s syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.
Wernicke’s Encephalopathy - Example Question
A 55 year old male is found confused on street by policeman. Hospital records document that he is a known to be a type 2 diabetic with previously DNAs to clinic and known poor compliance with medications. He also had two previous admissions to hospital, 2 and 10 years ago, for alcohol withdrawal. On examination, the patient is not orientated in time or place, scoring 0 out of 10 on abbreviated mental. He is able to follow your commands in lifting his upper and lower limbs during his neurological exams. All reflexes were present. He fails to follow your finger with his eyes on cranial nerve examination. His gait is grossly ataxic, as you noted when he tried to walk to the toilet against medical and nursing advice. His blood sugar is awaited. What is the diagnosis?
> Wernickes encephalopathy Delirium Miller-Fisher syndrome Hypoglycaemia secondary to anti-glycaemic overdose Acute ischaemic stroke
The patient presents with a triad of ophthalmoplegia, ataxia and encephalopathy, suggestive of Wernickes encephalopathy. The pathophysiology relies on an underlying thiamine deficiency, which is a key co-factor in energy metabolism, and is often deficient in alcoholics. Miller-Fisher syndrome is a key differential in this case: this is a variant of Guillain Barre syndrome presenting with ophthalmoplegia, ataxia and areflexia. Delirium and hypoglycaemia should not present with ophthalmoplegia.
HSV Encephalitis
Herpes simplex encephalitis
Herpes simplex (HSV) encephalitis is a common topic in the exam. The virus characteristically affects the temporal lobes - questions may give the result of imaging or describe temporal lobe signs e.g. aphasia
Features
fever, headache, psychiatric symptoms, seizures, vomiting
focal features e.g. aphasia
peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis
Pathophysiology
HSV-1 responsible for 95% of cases in adults
typically affects temporal and inferior frontal lobes
Investigation
CSF: lymphocytosis, elevated protein
PCR for HSV
CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients
MRI is better
EEG pattern: lateralised periodic discharges at 2 Hz
Treatment
intravenous aciclovir
The prognosis is dependent on whether aciclovir is commenced early. If treatment is started promptly the mortality is 10-20%. Left untreated the mortality approaches 80%
Anti-NMDA Receptor Encephalitis
Anti-NMDA receptor encephalitis is a paraneoplastic syndrome, presenting as prominent psychiatric features including agitation, hallucinations, delusions and disordered thinking; seizures, insomnia, dyskinesias and autonomic instability. Ovarian teratomas are detected in up to half of all female adult patients, particularly prevalent in Afro-Carribean patients1. MRI head can be normal but abnormalities can be visualised on FLAIR sequences in the deep subcortical limbic structures2. CSF may demonstrate pleiocytosis but can be normal initially.
Treatment of anti-NMDA encephalitis is based of immunosuppresion with intravenous steroids, immunoglobulins, rituximab, cyclophosphamide or plasma exchange, alone or in combination. Resection of teratoma is also therapeutic.
Anti-NMDA Receptor Encephalitis - Example Question
A 68 year old female presents via blue light ambulance to the emergency department with a first seizure, witnessed by her husband. He describes a sudden onset limb jerking lasting for around 6 minutes, associated with urinary incontinence and tongue biting, with a period of confusion and drowsiness immediately after. He is not aware of her having had any previous seizures, she has no other past medical history and does not take drugs on a medical history. He however does describe her to be ‘not quite herself’ over the past four weeks, when she appears to have been extremely agitated and occasionally extremely paranoid. He had thought it to be linked to her not feeling very well, during a period when she had complained of a ‘flu-like’ headache, generalised muscle ache and a non-productive cough.
You examine her, finding significant gait and limb ataxia with no truncal ataxia. Her blood tests are unremarkable except for positive anti-NMDA antibodies. Her MRI scan demonstrates swelling in bilateral limbic corticies and other no other intracranial abnormalities. She has declined a lumbar puncture and is thought to retain capacity.
Which investigation would most likely provide the underlying diagnosis?
> CT abdomen/pelvis with contrast Lumbar puncture Nerve conduction studies and EMG MRI spine Muscle biopsy
This middle aged woman has presented with seizures on a background of personality change, agitation, paranoia and cerebellar ataxia. The diagnostic test is her positive anti-NMDA antibody, with MRI confirm limbic encephalitis as a result of a paraneoplastic syndrome. The underlying diagnosis is classically an ovarian teratoma, presenting antigens to the bodys immune system similar to the brain limbic areas, driving an immune-related encephalitis. Treatment requires immunosuppresion with intravenous steroids, immunoglobulin’s or plasma exchange, in addition to removal of the underlying tumour by surgery.
Autoimmune Limbic Encephalitis Diagnosis - Example Question
A 43-year-old man is apprehended by the police after a violent assault outside a pub. He is brought to the attention of the duty psychiatrist because he is extremely confused and agitated. He repeatedly says that his wife is having an affair with the Prime Minister. He believes this to be true because of a message encoded in the traffic lights. He also mentions that he has not slept in the last two days.
The psychiatric assessment is interrupted when he has a tonic-clonic seizure, which self-terminates in 3 minutes. He is taken to the local Accident and Emergency department and reviewed by the medical team.
The medical SHO manages to contact his wife, who reports that he is normally fit and well and she last saw him when he left for work five days ago. At that time he appeared normal but complained of a headache, and took some ibuprofen.
During the clerking, he is noted to have repetitive chewing movements of the mouth. Again, the assessment is interrupted by a tonic-clonic seizure which does not terminate after 10mg of intravenous diazepam. After 15 minutes he is loaded with phenytoin. He continues to fit so is intubated and transferred to the Intensive Care Unit. Termination of seizure activity is only achieved after induction of general anaesthesia with thiopentone.
What is the most likely diagnosis?
Schizophrenia Fronto-temporal dementia Acute intermittent porphyria Post-ictal psychosis > Autoimmune limbic encephalitis
Autoimmune limbic encephalitis presents with acute or sub-acute cognitive dysfunction, behavioural changes, and seizures. A number of specific antibody-related syndromes have been described. The description given here is suggestive of anti-NMDA receptor encephalitis, with a prodromal headache followed by prominent psychiatric features, with orofacial dyskinesias, insomnia, and progression to seizures.
Schizophrenia is a common cause of psychosis but the seizures should point away from a psychiatric disorder towards an organic brain pathology.
Fronto-temporal dementia is a slowly progressive condition.
Acute intermittent porphyria may cause a range of neurological manifestation including psychosis and seizures, but there are no features here that point specifically to this diagnosis.
Post-ictal psychosis is a rare manifestation of the post-ictal state, typically in patients who have had epilepsy for some time. The rapid development of psychosis and seizures in a previously well person should prompt the search for an alternative diagnosis.
Autoimmune Limbic Encephalitis - Example Question
A 62 year old Afro-Carribean female is brought to the Emergency Department by husband after a 3 day history of unusual, odd behaviour at home. The family had hosted a dinner party that evening and the patient was reported to have been very disinhibited, agitated and describing hallucinations around her guests. In the past 3 weeks, she had two episodes of generalised seizures witnessed by her husband, each lasting for up to 5 minutes before spontaneously terminating, associated with urinary incontinence and tongue biting. She has no history of epilepsy and is not on any regular medications, but was diagnosed with ovarian teratoma two years ago. On examination, she has no focal neurology but you note a dystonic orofacial movement disorder. A CT head was unremarkable, with no acute infarct, haemorrhage or space occupying lesion demonstrated.
Which investigation is most likely to produce the diagnosis?
MRI head Lumbar puncture > Anti-NMDA receptor antibodies Anti-MuSK antibodies Anti-GM1 antibodies
The syndrome described is strongly suggestive of an autoimmune-mediated limbic encephalitis.
MRI of HSV Encephalitis
Hyperintensity of the affected white matter and cortex of the MEDIAL TEMPORAL LOBES and INSULAR CORTEX
Medial temporal lobe and insular cortex - Think HSV Encephalitis
Most common OCULAR abnormality in Wernicke’s Encephalopathy?
Nystagmus
Japanese Encephalitis - Example Question
Japanese encephalitis
Japanese encephalitis is the most common cause of viral encephalitis in South East Asia, China the Western Pacific and India, with approx. 50,000 cases annually. It is a flavivirus transmitted by culex mosquitos which breeds in rice paddy fields. The reservoir hosts are aquatic birds, but pigs are an amplification host and therefore close domestic contact with pigs is a risk factor.
The majority of infection is asymptomatic.
Clinical features are headache, fever, seizures. Parkinsonian features indicate basal ganglia involvement. It can also present with acute flaccid paralysis.
Diagnosis is by serology or PCR. Management is supportive.
Prevention is a vaccine and there are a variety of different types.
Example Question:
A 17 year old girl presents to A&E accompanied by her anxious mother. She was born in England, but both her parents were born in a rice growing community in rural China. She has recently returned from a holiday where she was visiting her family in China. They live on a farm where she had close contact with dogs, sheep and pigs.
She arrived home one week ago. She was taking Mefloquine for malaria prophylaxis.
She was complaining of fever and a headache yesterday. Today she has been confused and disorientated.
She is previously fit and well, she has had all her immunisations according to the UK immunisation schedule, with normal growth and development. She does well at college and is a keen member of her college canoe club. She has no allergies.
On examination she is febrile at 38.9°C but haemodynamically stable. She appears confused and has an obvious difficultly walking. Examination of her cranial nerves is difficult but unremarkable. She has normal power and increased tone in her arms, which is more pronounced on the left side, with hyperreflexia bilaterally. She has several writhing involuntary movements of her upper limbs during the consultation.
A CT scan shows hypodensity in the thalami and basal ganglia bilaterally, more pronounced on the left side.
A lumbar puncture reveals a lymphocytic CSF with a raised protein.
What is the most likely diagnosis?
Herpes Simplex Encephalitis > Japanese Encephalitis Alcohol consumption Rabies Mefloquine toxicity
