The diseases Autoimmune Encephalitis and CJD are quite rare.

Though the topics are quite big enough to discuss we try to review this to the possible extent.

CJD: Occurs 1-2 per million population. It is a prion disease.  It is not known how the disease began. It was presumably through Cannibalism of a person with CJD. Women and children are more involved as they consume brain and spinal cord which contains more prions.cessation of ritual of cannibalism eliminated the disease. It was seen in Papua New Guinea along with kuru because of the ritual of Endocannibalism.   Non-human spread like beef eating contaminated with BSE is important cause in developing vCJD. CJD is commonly seen in beyond 50 years of age group most of the times. Famillial and variant type of CJDs may be seen in the early age group. There are 4 types of CJD's identified.

1. Sporadic -60-80% more common. No apparent reason was identified. May be through spontaneous transformation of the prion protein Prpc into Pr^sc
2. Variant CJD - less common, transmitted through the animal flesh eating which is infected with BSE.
3. Genetic CJD - occurs in the early age group and commonly seen in the family members. This comes to about 7.5 percent and has Autosomal dominant inheritance.

The genetic CJD conditions are:

1. A) GERSTMANN-STRUSSLER-SCHEINKER SYNDROME (GSS)
2. B) FATAL FAMILIAL INSOMNIA.
3. Iatrogenic- This occurs most commonly during the surgeries where they do the duroplasty from the affected person and corneal transplant, injection of pituitary growth hormone of infected person and skin transplants from infected people.

Phenotypic Variants¹-

1. Amyotrophic variant: Amyotrophic lateral sclerosis type of presentation initially.
2. Brownell-Oppenheimer variant: Initial presentation is cerebellar ataxia.
3. Heidenhain variant: Initial visual symptoms like impaired vision, visual hallucinations, and loss of vision.
4. Stern - Garcin variant: Initial extra pyramidal symptoms.

The commom clinical presentation are behavioural disturbances, memory loss which is progressive. The patient may have involuntary movements like dystonia of the limbs, catatonia and incoordination. Some patients may have blurring of vision and blindness. They may have multiple seizures, status epilepticus and more common myoclonic jerks. These patients detoriate fast and they usually die within 1-2years.

Diagnosis:

1. The clinical presentation as described above
2. CSF analysis which show lymphocytic cellular response, Raised protein and positive protein 14-3'-3. Recently they use t -tau and S 100 β as markers which are more sensitive².
3. Radiological:  Hyperintense signals in bilateral ganglionic regions and Ribbon like Hyperintense lesion along fronto parietal and occipital regions along the cortex.Grey matter involvement is very common and probably diagnostic
4. Recently CSF and / or olfactory mucosal real time queaking induced conversion seeding assays are more sensitive than 14-3-3 protein.But yet to be evaluated further.

The confusion with Autoimmune encephalopathy and CJD is because of the early clinical manifestations which  are similar which we have already discussed. The early identification and evaluation for the antibodies and proper management make the patient do better and survive well.

Autoimmune encephalopathies⁴:  There are several Autoimmune encephalopathies which came into picture in the last 10 years. Some of the auto immune encephalitis are 1. APMDAR  2. LGI 1  3.GABA B R  4.CASPAR 2   5. GABA A R 6. MOG  7. GLYCINE R 8. AMPAR  9. DPPX  10. IGLON 5

The earliest clinical presentation is same in both the conditions making us to confuse in the early clinical diagnosis. Among all these Autoimmune encephalopathies, Hashimoto's Encephalopathy is more common and also called as steroid responsive encephalopathy. All these encephalopathies have common symptomatology but 1-2 symptoms which are specific for AE which should be identified so that diagnosis is made easy. These Autoimmune Encephalitis divided mainly into 2 types

1. Tumoral where in AE is associated with a tumor elsewhere and removal of the tumor only can improve the encephalitis.
2. Non-Tumoral- Here AE is not associated with any tumor supposed to be idiopathic. Those cases which are not associated with tumor they respond very well to immunotherapy whereas tumoral cases unless otherwise the tumor is removed, they will not respond.

The other end of the spectrum which produce AE is those which have antibodies to intracellular antigens which are tumoral antibodies which respond to removal of the tumor such as anti HU antibodies and the other are extra cellular antigens which produce antibodies to ion channel receptors and other proteins such as NMDA receptors and are non-tumoral and respond well to immunotherapy.

Other types are intermediate antibodies to intracellular synaptic proteins such as GAD65.

The other one is antibodies less clear as in ADEMand Lupus cerebritis.

Clinical clues to recognize autoimmune encephalitis³:
PSYCHOSIS:  NMDA R, AMPA R, GABA B R

DYSTONIA AND CHOREA: NMDA R, D2R

HYPER EKPLEXIA: Gly R

STATUS EPILEPTICUS: GABA A and GABA B R.

NEW ONSET DIABETES: GAD65

FACIOBRACHIAL DYSTONIC SEIZURES: LGI 1

NEUROMYOTONIA, FASCICULATIONS, SPASTICITY:  CASPR 2.

DIAGNOSIS: 1. Ig G testing should be done both in serum and CSF.The sensitivity is 85%, vs120%.

Lymphocytic pleocytosis and elevated protein are seen.

EEG:  Variable.Slowing is commonly seen.

One third develop Deltabrush appearance.

MRI:  Usually normal.

May show suble mesial hyppocampal FLAIR hyperintesities and multifocal Grey and white matter hyperintesities.

Treatment: Those patients with nontumoral antibodies positive will respond well to immunotherapy.

This includes

1. Methylprednisolone 1 gm daily for 5 days.
2. IV Ig 400mg per kg body weight per day for 5 days.
3. Plasmapheresis
4. Mycophenalate, Azathioprine, Rituximab and cyclophospamide can be as second line drugs.

In the present case the patient has symptomatology common to both AE and CJD which made us to confuse in the early diagnosis. The identification of the TPO antibodies further made us to confuse more with AE. Hence, we treated with Methy prednisolone as there is no response, we have treated with IV IG. As there is progressive deterioration of the sensorium, EEG findings, CSF findings with positive protein 14-3-3 and MRI findings made us to confirm the diagnosis of CJD. Though the brain biopsy is the confirmation it’s difficult procedure in the living and the above three criteria satisfies the diagnosis. Some people suggest Tonsillar biopsy in vCJD cases.    We have managed symptomatically.  There is improvement in seizure control to some extent but there's progressive deterioration in sensorium and comatosed. As the patient has deteriorated further, she was discharged at request.

Take home message: - Patients presenting with behavioural disturbances, progressive memory impairment, involuntary movements and seizures should be evaluated thoroughly for the presence of autoimmune antibodies and treat accordingly as these patients respond very well to autoimmune therapy in Non-Tumoral cases and removal of the tumor in tumoral cases.

The progressive deterioration of sensorium, positive CSF findings, MRI findings and EEG findings should be considered in the diagnosis of CJD. As this disease has no treatment and succumbs to death in 1-2 years. Symptomatic treatment is the only choice.