Case presentation on subacute sclerosing panenecephalitis pediatrics

Case presentation on sspe

1. MORNING MEETING DR. DANISH FCPS TRAINEE @ CDF HOSPITAL

2. BIODATA AND PRESENTING COMPLAIN 3 year old male child weighing 14kg resident of thatta admitted via ER with c/o Inability to walk and stand for 14days Abnormal movements for 14days

3. HOPC A 3 year old boy, with normal growth and development, came with a 14days history of inability to walk and continuous involuntary jerky movements of the body including the head. His symptoms started 15days before, following a unprovoked sudden generalized seizure for about 10mins and then he became nonambulatory . His mother also noticed a subsequent progressive mental decline.

4. PAST MEDICAL HISTORY Measles at the age of 1 year, remained admitted for 10 days, was on ventilator support for 3 days BIRTH HISTORY Assisted conception after 5 years of marriage, SVD, Term, Twin gestation (non identical) IMMUNIZATION HISTORY Unvaccinated DEVELOPMENTAL HISTORY Gross Motor, Fine motor, Social and Speech according to age FAMILY HISTORY

5. PAST SURGICAL HISTORY TRANSFUSION HISTORY DRUG HISTORY PERSONAL HISTORY SOCIOECONOMIC HISTORY

6. EXAMINATION On Examination, alert looking child with abnormal asymmetrical continuous jerky movements of both limbs lying on bed with following vitals: HR: 96bpm R/R 30breaths/min SpO2 at room air: 98% Temperature: 98 F BP: 96/52 mmHg (on 50th percentile respectively) SUBVITALS: A+, J-, CY-, D-, Ed-, Cl-

7. ANTHROPOMETRIC MEASUREMENTS Weight: 14 kg (between 25th and 50 th percentile) (SDS -0.44) Height: 95 cm (on 50 h percentile) (SDS -0.06) OFC: 50 cm (SDS -0.061)

8. CNS EXAMINATION GCS: 9/15 E4V1M4 PUPILS: BERL FUNDOSCOPY: NORMAL

9. CNS EXAMINATION OLFACTORY NERVE: (could not be assessed) OPTIC NERVE: (Pupils berl, visual acuity and field of vision could not be assessed) OCCULOMOTOR, TROCHLEAR, ABDUCENT NERVE: Intact TRIGEMINAL NERVE: Intact FACIAL NERVE: Intact VETIBULOCOCHLEAR NERVE: (could not be assessed) GLOSSOPHARYNGEAL AND VAGUS NERVE: Intact gag reflex ACCESSARY NERVE: (could not be assessed) HYPOGLOSSAL NERVE: Intact

10. CNS EXAMINATION RUL RLL LUL LLL TONE Normal Normal Normal Normal POWER 3/5 3/5 3/5 3/5 REFLEXES +2 +2 +2 +2 PLANTARS - UPGOING - UPGOING

11. CNS EXAMINATION SENSORY SYSTEM EXAMINATION: INTACT CEREBELLAR SIGNS: NO NYSTAGMUS, REST OF THE SIGNS COULD NOT BE ASSESSED

12. SYSTEMIC EXAMINATION CVS EXAMINATION: INTACT ABDOMINAL SYSTEM EXAMINATION: INTACT RESIRATORY SYSTEM: INTACT

13. DIFFERENTIAL DIAGNOSIS SUBACUTE SCLEROSING PANENCEPHALITIS NEURODEGENERATIVE DISORDER (METACHROMATIC AND ADRENOLEUKODYSTROPHY) PROGRESSIVE MYOCLONIC EPILEPSY

14. INVESTIGATIONS CBC Hb 10.6 TLC 7.8 N 43% L 50% M 04% E 03% PLT 366 ANC 3354 UCE UREA 35 Cr 0.3 Na 139 K 3.8 Cl 104 Ca 9.0 Mg 1.8

15. MRI BRAIN WITH CONTRAST

16. MRI BRAIN WITH CONTRAST Diffuse leptomeningeal enhancement Hyper intense signals seen on T2 and FLAIR images in bilateral centrum semiovale , posterior parietal and frontal deep white matter, midbrain and pons. No evidence of restriction on DW1/ADC mapping Findings are suggestive of SSPE

17. ELECTROENCEPHALOGRAM

18. ELECTROENCEPHALOGRAM Abnormal EEG in view of frequent generalized high voltage delta bursts intermixed with sharp component followed by 0.5 to 2.5 seconds of electrodecremental . Suggestive of generalized seizure disorder (this pattern could be seen in SSPE).

19. CSF FOR OLIGOCLONAL BANDS Present in CSF indicative of intrathecal IgG synthesis, No bands or non matching bands detected in serum.

20. CSF FOE MEASLES IgG ANTIBODIES Patient Antibody Index 2.60- Positive

21. MANAGEMENT: ADMIT TED MAINTAIN IV LINE AT ROOM AIR, NASOGASTRIC TUBE FEEDING VITAL MONITORING IV ANTIBIOTICS (CEFTRIOXONE 75MG/KG OD) IV ANTI EPILEPTICS (LEVITRACETAM 60MG/KG/DAY 8H, CLONAZEPAN 0.01MG/KG/DAY AND SODIUM VALPROATE 60MG/KG/DAY 8H) IV ANTI PYRETICS LUMBAR PUNCTURE CONSENT OBTAINED MRI BRAIN AND EEG KETO DIET AND ISOPRINOSINE

22. FINAL DIAGNOSIS: SUBACUTE SCLEROSING PANENCEPHALITIS

23. DISCUSSION: Subacute Sclerosing Panencephalitis (SSPE) is a rare complication due to persistent measles infection. This neurological sequela typically presents in early adolescence and has a progressive course with a high mortality rate. Vaccination implementation has been effective in reducing the number of Measles cases, thereby reducing cases of SSPE. However, measles remains endemic in many countries with poor access to vaccinations. Also, there has been a re-emergence of measles in industrialized countries due to vaccination refusal

24. ETIOLOGY Subacute sclerosing panencephalitis is caused by the measles virus, which is a single-stranded RNA virus of the  Paramyxoviridae  family. It is one of the most contagious diseases, measles can be transmitted to 12 to 18 persons from one infected individual. Transmission occurs through aerosols from person to person. Many complications can occur both acutely and chronically, some of which are neurological complications, like SSPE. Children less than five and adults over the age of 20 are at higher risk of death.

25. EPIDEMIOLOGY Generally, 4 to 11 per 100,000 cases of measles result in SSPE. This number goes up to 18 per 100,000 cases if the child was less than five years old when primarily infected with measles. It appears to have a higher prevalence in males, with later onset and increased latency in females. Risk factors for SSPE include being from a rural area or poverty-stricken area, overcrowding, multiple siblings, or higher birth order due to an increased chance of exposure and infection at a younger age (less than 5). SSPE tends to have an earlier onset and a more fulminant course in individuals with acquired immunodeficiency syndrome, children whose mothers had measles during pregnancy, or if there was an incomplete transfer of measles antibodies during gestation.

26. PATHOPHYSIOLOGY The typical immune response to infection starts with T-helper 1 cells that release interferon-alpha and IL-2. These cytokines help to eliminate the viral infection from cells. The humoral response then plays a role in making antibodies for long term protection from the virus. These antibodies will trigger T-helper 2 cells that release large amounts of IL-4 and a small amount of IL-2 and interferon-alpha. It is a possibility that SSPE is the result of a poor cellular immune response. There is evidence to suggest that patients who go on to develop SSPE have a reduced cellular immune response and an elevated humoral immune response, which would prevent the patient from completely eradicating the virus. [4]

27. CLINICAL MANIFESTATION The course of SSPE has been divided into stages, each of which describes a certain phase of the disease. Stage I includes many personality or behavioral changes, such as irritability, dementia, lethargy, social withdrawal, or speech regression. Stage II is made up of the progressive decline in motor function, including myoclonus, dyskinesia, and dystonia. Stage III consists of patients who have progressed to extrapyramidal symptoms, posturing, and spasticity. Lastly, stage IV occurs when patients develop akinetic mutism , autonomic failure, or enter a vegetative state

28. CLINICAL MANIFESTATIONS Atypical presentations of SSPE can include psychiatric symptoms, seizure disorders poorly controlled with medication or solely extrapyramidal symptoms. When atypical symptoms are present, SSPE tends to have a fulminant course with neurological deficits occurring in the first 3 months or death within 6 months in about two-thirds of cases. Having the measles virus before the age of 2, increased viral virulence and coinfection with other viruses are risk factors for a more fulminant, atypical course.

29. DIAGNOSTIC CRITERIA Modified Dyken’s criteria is developed for diagnosis of SSPE 2 major and 1 minor criteria is required

30. TREATMENT No cure exists for subacute sclerosing panencephalitis . Most treatments are aimed at symptom reduction. Inosine pranobex  is an oral antiviral that halts viral replication and immunomodulator . The dosing is 100mg/kg/day divided into three doses throughout the day with a maximal dosage of 3000mg/day. This therapy is known to cause elevated uric acid in urine and serum samples, as well as occasional nausea

31. TREATMENT Interferon-alpha (INF-alpha)  is another mode of therapy typically used with Isoprinosine. It is an immunomodulator administered via the intrathecal route every week. Maximal efficacy of interferon-alpha can only be achieved with long-term treatments. Some studies have shown that there is no advantage to daily Isoprinosine plus weekly INF-alpha versus Isoprinosine monotherapy . Ribavirin , a nucleotide analog, has also been tried as a supportive treatment. Little success was noted, and it seemed to only mildly benefit patients when used in conjunction with INF-alpha.

32. TREATMENT As an alternative treatment, several case reports recommend a ketogenic diet. There has been some variable success with this in reducing myoclonus symptoms in patients with SSPE who have failed other treatment options. This particular diet is neuroprotective in that it reduces oxidative stress, improves mitochondrial activity, and suppresses factors that induce apoptosis.

33. TREATMENT MODALITIES UNDER STUDY Other therapies that are currently being studied in vitro include antiapoptotic agents and small interfering RNA. siRNA appears to inhibit viral replication in cells but has not been studied as therapy in humans yet. Other studies have recommended the development of therapies that could block membrane fusion, which could potentially stop the progression of CNS infections by the measles virus.

34. PREVENTION At this moment, preventing SSPE from developing is the best treatment option. Vaccination for the measles virus is a very safe and effective way to prevent initial infection. The vaccination is separated into two doses, one given at 12 to 15 months and the second given between the ages of 3 to 5 years. Vaccination cannot be given to anyone who is immunosuppressed because it is a live-attenuated vaccine. WHO recommends administering the vaccine to HIV-positive patients in the absence of severe immunosuppression. 95% must demonstrate immunity with anti-measles antibodies to completely eradicate the measles virus from a population. In the last few years, there has been a re-emergence of the measles virus in industrialized countries. This is largely attributed to reduced vaccination due to vaccine hesitancy

35. PROGNOSIS The mortality rate is exceptionally high in the case of SSPE, about 95%, while the remaining cases undergo spontaneous remission. The average life span after the initial presentation is about 3.8 years, with a range of 45 days to 12 year.

36. COMPLICATIONS SSPE is a complication of chronic CNS infection by the measles virus. A patient with SSPE experiences a progressive course of neurological deficits, which ultimately results in death. Treatments that attempt to prolong and improve the quality of life can have some side effects/complications. Interferon-alpha can cause flu-like symptoms or produce a clinical relapse secondary to antibodies to the interferon. Ribavirin can produce oral mucositis , headache, fatigue, and reversible anemia.