Hashimoto Encephalopathy

Embed Size (px)

Citation preview

Hashimoto's encephalopathy:An Under Diagnosed EntityDr. Ibrahim Mokhtar Consultant EndocrinologistKing Khalid Hospital , Najran, Saudi Arabia Sunday 01/01/2012

Any one knows this gentle man ?

Dr. Hakaru Hashimoto

In 1912 Hashimoto described four patients with a chronic disorder of the thyroid, which he termed struma lymphomatosa. y The thyroid glands of these patients were characterized by diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and an eosinophilic change in some of the acinar cellsy

Hashimoto's Thyroiditis

Pathology of Hashimoto's thyroiditis. In this typical view of severe Hashimoto's thyroiditis, the normal thyroid follicles are small and greatly reduced in number, and with the hematoxylin and eosin stain are seen to be eosinophilic. There is marked fibrosis. The dominant feature is a profuse mononuclear lymphocytic infiltrate and lymphoid germinal

center formation

The disease has been called Hashimoto's thyroiditis, chronic thyroiditis, lymphocytic thyroiditis, lymphadenoid goiter, and recently autoimmune thyroiditis. y Classically, the disease occurs as a painless, diffuse enlargement of the thyroid gland in a young or middleaged womany

Hashimoto's Thyroiditis

y y y y y y y y

Euthyroidism and goiter Subclinical hypothyroidism and goiter Primary thyroid failure Hypothyroidism Adolescent goiter Painless thyroiditis or silent thyroiditis Postpartum painless thyrotoxicosis Alternating hypo- and hyperthyroidism

Presentations of Hashimoto's Thyroiditis

Hashimoto's encephalopathy or encephalitis is a very rare complication of Hashimoto's thyroiditis y This condition was first described in 1966 y Patients with this encephalopathy are usually euthyroidy

Hashimoto's encephalopathy

y y y y

It is treatable, steroid-responsive, Progressive or relapsing encephalopathy Associated with elevation of thyroid specific autoantibodies It belongs to a group of neurologic disorders called autoimmune encephalopathy

Hashimoto's encephalopathy

Not clearly understood y Sawka et al. reported that this condition is not caused by thyroid dysfunction or antithyroid antibodies but represents an association of an uncommon autoimmune encephalopathy with a common autoimmune thyroid diseasey

Hashimoto's encephalopathy :Pathogenesis

y

The exact pathophysiology of Hashimotos encephalopathy is unknown, but an autoimmune mechanism has been suggested because of its higher prevalence in females, fluctuating course, association with other autoimmune disorders and dramatic improvement following corticosteroid therapy.

Hashimoto's encephalopathy :Pathogenesis

y

Shaw et al. suggested that there may be a shared, yet unidentified antigen between the brain and thyroid gland, and it is possible that the same antibody is reactive against a common neuronal and thyroid antigen, resulting in thyroiditis and Hashimotos encephalopathy.

Hashimoto's encephalopathy :Pathogenesis

y

The focal and global cerebral symptoms may be attributed to autoimmune-mediated cerebral vasculitis, with or without immune complex deposition,and an antineuronal antibody-mediated mechanism

Hashimoto's encephalopathy :Pathogenesis

y

Vasculitis, if severe, may result in ischemia or infarction which has been shown on CT scan or MRI studies

Hashimoto's encephalopathy :Pathogenesis

y

immunoinflammatory effect of Hashimotos encephalopathy resulting in ischaemic demyelination or axonal changes with delayed evoked potentials

Hashimoto's encephalopathy: Pathogenesis

y

y

y

Identification of antibodies to brain specific antigens may disclose the real pathogenesis of this condition Antibody to -enolase has been identified in some patients but this antibody is also frequently found in other autoimmune diseases. Recently, autoantibodies against the amino (NH2)-terminal of -enolase (referred to as NAE) were reported to be highly specific in sera from a limited number of HE patients.

Hashimoto's encephalopathy :Pathogenesis

y

Steroid reversible cerebral hypometabolism was recently documented by SPECT scanning in this condition.

Hashimoto's encephalopathy :Pathogenesis

y

It may present withSubacute or acute encephalopathy, Seizure, Myoclonus, Tremulousness, Stroke-like episode, Amnesia or dementia.

y y

Some patients suffer from a significant residual disability It is associated with abnormal EEG and high CSF proteins without pleocytosis.

Hashimoto's encephalopathy :Presentation

y

In Hashimotos encephalopathy, various EEG abnormalities have been described which included diffuse slowing, mesial temporal lobe epileptic focus during ictus, diffuse slowing with triphasic discharge, and non-specific changes

Hashimoto's encephalopathy :Presentation

y

SPECT studies in Hashimotos encephalopathy have shown global hypoperfusion or focal hypoperfusion, associated with focal abnormalities on CT scan

Hashimoto's encephalopathy :Presentation

Hashimoto's encephalopathy : Case study

y

y

y y y

A 42-year-old lady had suffered from behavioral abnormalities (irritability, restlessness and myoclonic jerks) for 2 weeks. The myoclonic jerks involved the extremities, 34 attacks per hour, were not associated with falling, and were absent during sleep. Four days before hospitalization, she developed progressive unsteadiness of gait and two attacks of generalized tonic- clonic seizures, each attack lasting for 23 min. Following seizure, she was febrile (38.9C) and developed altered sensorium. There was no history of hypertension, diabetes mellitus or collagen vascular disease. No family member suffered from a similar illness

Hashimoto's encephalopathy : Case study 1QJM (2003) 96 (6): 455-457. doi: 10.1093/qjmed/hcg075 (2003) 455-457. doi: 10.1093/qjmed/hcg075

y

y y y y y y y y y

On examination, the patient was well-built, her pulse was 100 bpm and regular, BP was 150/90 mmHg, temperature 38.9C and respiratory rate 18 breaths/min. She was comatose, and her Glasgow coma scale score was 6. Pupils were normal size and reactive to light. Corneal reflex, Dolls eye movement and gag reflex were present. There was no facial asymmetry. She moved all four limbs on painful stimuli. Muscle tone was increased in both upper and lower limbs. Biceps, triceps, knee and ankle reflexes were exaggerated and planters extensor bilaterally. Neck was supple. There was no hepatosplenomegaly and examinations of heart and lungs were normal. She had a diffuse goitre without any bruit.

Hashimoto's encephalopathy : Case study 1

y

y

y y y

Laboratory tests revealed total white blood cell count of 13 500/mm3 with 78% polymorphic, Hb 11 g%, ESR 57 mm for the first hour, and platelet counts 1.73 lac/mm3. Her fasting blood sugar was 100 mg/dl, BUN 18 mg/dl, serum creatinine 1 mg/dl, serum sodium 135 meq/l and serum potassium 3.5 meq/l. Serum calcium, alkaline phosphatase, serum proteins and urinalysis were normal. Radiograph of chest, electrocardiogram and cranial MRI were also normal. Cerebrospinal fluid revealed 49 mg/dl protein, 95 mg/dl sugar and no cells

Hashimoto's encephalopathy : Case study 1

y

y y

y

Thyroid function test revealed T3 0.87 (normal = 1.3 2.8) mmol/l, T4 75.84 (normal = 60160) mmol and TSH 4.17 (normal = 0.35.0) mmol. Thyroid microsomal antibody was present at 1/25 600 dilution. Electroencephalography on the fifth day of altered sensorium revealed diffuse theta to delta slowing without any right to left asymmetry. There was no epileptiform discharge. Her tibial somatosensory evoked potentials (right 16 ms, left 18 ms) and central motor conduction time to lower limbs (right 12.4 ms, left 12.6 ms) were normal.

Hashimoto's encephalopathy : Case study 1

She was treated with intravenous antibiotics, sodium valproate 300 mg three times daily and hydrocortisone 100 mg intravenously 6-hourly, following which she made a remarkable recovery. y On the fourth day of hydrocortisone therapy, she was conscious and conversed coherently. y There was no recurrence of seizure and myoclonic jerks. y She was prescribed oral prednisolone 40 mg daily, and sodium valproate continued.y

Hashimoto's encephalopathy : Case study 1

y y y y y y y

Further investigation revealed absence of antinuclear antibody and antiparietal cell antibody. Fine-needle aspiration cytology of the thyroid swelling showed lymphocytic thyroiditis. Her P100 latency of visual evoked potentials were prolonged on both sides (right 112 ms, left 110 ms). A SPECT study carried out on third week revealed right temporoparietal hypoperfusion . Repeat EEG after 15 days of corticosteroid therapy was normal. She was discharged after 28 days of hospital stay. On discharge, her mini-mental scale score was 21 which was normal, as she was illiterate. Her pyramidal sign disappeared, and she could walk normally and perform all the activities of daily living.

Hashimoto's encephalopathy : Case study 1

Single photon emission computed tomography (SPECT) scan of the patient showing right temporoparietal hypoperfusion

The diagnosis of Hashimotos encephalopathy was based on : y Clinical features, y Thyroid microsomal antibody, y FNAC of chronic lymphocytic thyroiditis y And response to corticosteroid therapy.y

Hashimoto's encephalopathy : Case study 1

The presence of behavioral abnormality, myoclonic jerk, and walking difficulty in our patient simulated Cruetzfeldt-Jacob disease (CJD), but the EEG revealed diffuse slowing; in CJD, characteristic periodic discharges are seen. y The dramatic improvement in clinical symptoms and normalization of EEG following corticosteroid further ruled out the possibility of CJD.. y The triphasic waves and background slowing in our patient normalized after 2 weeks of corticosteroid therapy, and the improved EEG was associated with improvement in the patients clinical conditiony

Hashimoto's encephalopathy vs. CJD

Subacute encephalopathies caused by autoimmune or inflammatory mechanisms, y Have characteristic clinical and serological features y Recognized by the association with autoantibody markers y And/or clear response to immunomodulatory treatment.y

Autoimmune encephalopathies

y

IncludesMorvan syndrome, Paraneoplastic limbic encephalitis (PLE), and Nonparaneoplastic autoimmune limbic encephalitis Hashimoto's encephalopathy

Autoimmune encephalopathies

y

y

Morvan syndrome presents with behavioral changes, hallucinations, severe insomnia , autonomic hyperactivity and neuromyotonia (spontaneous muscle activity). Limbic encephalitis is characterized by short-term memory impairment, complex partial temporal lobe seizures and psychiatric symptoms. Signal abnormalities in the mesial temporal lobes without contrast enhancement are the typical MRI findings

Autoimmune encephalopathies

y

Hashimotos encephalopathy (HE) has been described as an encephalopathy, with acute or subacute onset, accompanied by seizures, tremor, myoclonus, ataxia, psychosis, and stroke-like episodes, with a relapsing/remitting or progressive course

Take Home Message

HE patients have positive antithyroid antibodies, y Are usually in euthyroid or a subclinical hypothyroid state, y Have elevated cerebral spinal fluid (CSF) protein, y And have nonspecific electroencephalogram (EEG) and imaging abnormalities y In the absence of CNS infection, tumor, or stroke.y

Take Home Message

Hashimotos encephalopathy but should be considered in the differential diagnosis of patient presenting with encephalopathy , not least because of the therapeutic potential. y Corticosteroid therapy results in quick recovery.y

Take Home Message

Thank YouHave A Good Day