This is a 10 year old female who presents to the office with a chief complaint of clumsiness and blurred vision. She had been well until approximately 2 weeks ago when she noticed a loss of sensation and strength in her left leg, a rapid deterioration in vision, and a decrease in coordination. There is no history of fever, vomiting, or seizures. One year prior to this event, she presented to the hospital with poor coordination, dizziness and headaches. A left hemiplegia was noted as well as an asymmetric gait. A full recovery was made 5 days later, and she was discharged from the hospital without further treatment or a definite diagnosis.
Exam: VS are normal. Her weight, height, and head circumference are all at the 50th percentile. She is alert but subdued. Her HEENT exam is notable for severe visual loss and pale optic discs on funduscopy. Her heart, lungs, and abdomen are normal. She is noted to have a hyporeflexive paraparesis noted on the left.
She is hospitalized. A CT scan shows slightly enlarged ventricles, and an MRI scan shows multiple lesions in the periventricular white matter and cerebellum. Pattern visual evoked responses showed markedly delayed latencies. She is treated with corticosteroids and a full recovery results within a few weeks. Over the next 3 years, she has 2 more attacks with symptoms of right hemiplegia and bilateral visual loss. At the age of 15, she continues to be followed and has shown no further episodes.
Multiple sclerosis (MS) is an uncommon demyelinating disease characterized by focal disturbances in CNS function that usually follows a relapsing and remitting course. Because MS is known to most commonly affect adults in their 20's to 40's it is often an overlooked diagnosis in children. 3-5% of all MS cases are, however, diagnosed in patients below the age of 16 years, with 80% of these cases found between 10-15 years of age.
Although the exact cause of MS is unknown. It has been suggested that its etiology is multifactorial. One popular view is that MS is initiated by a viral infection in early life that alters a susceptible patient's immune status, thus predisposing him/her to develop an autoimmune CNS reaction to systemic infections. Although this is a widely held view, efforts to actually identify an infectious agent have been unsuccessful. In addition to speculation about a viral etiology, it has also been noted that MS occurs 10-20 times more in families of a MS patient than in the general population (1). There also appears to be a higher risk in females (2:1), people of western European descent, and those who lived in temperate (cold) climates before the age of 15. Thus it is believed that environmental (viral) as well as hereditary factors, a disordered autoimmune response, and the age of the individual at exposure plays a role in the pathogenesis.
The pathophysiology of the various neurological manifestations found in MS can be explained by multiple lesions disseminated throughout the CNS that spontaneously improve. Consequently, this also explains why the combination of signs and symptoms are limitless and why the symptoms often remit after a period of time.
Many of the clinical manifestations of childhood onset MS are similar to adult-onset MS (1). Table 1 below shows some of the symptoms found in the initial episode of MS in a study analyzing 56 children with MS. In general, visual disturbances such as blurring and diplopia are common in childhood MS with one study finding optic neuritis in 25-70% of children with MS (2). Paresthesia, motor disturbances, unstable gait, ataxia, vertigo, headaches, and sphincter problems also seem to predominate in childhood onset MS. Ghezzi et al. found that of 149 children who were diagnosed with MS before the age of 18, 25% had brainstem dysfunction, 18% had motor and sensory disturbances, and 9% had cerebellar disturbances (2). Transiently impaired consciousness and slowly progressive dementia have also been found in a significant number of children with MS (1).
Table 1: Number of children (out of 56) with these symptoms during the initial episode of MS (1):
Ataxia or muscle weakness: 31
Disturbance or vision (blurring, diplopia, blindness): 19
Numbness or paresthesia: 13
Dizziness, headache, vomiting: 10
Urinary incontinence: 2
Facial weakness: 1
Hearing loss: 1
Partial seizures: 1
While there are many similarities found between childhood and adult onset MS, there are some clinical differences. Bye et al. found a higher incidence of partial seizures in childhood onset MS (3) and brainstem dysfunction had also been noted to be more frequent at the first attack in children. Vestibular symptoms, however, were noted to be less common in childhood MS (3).
There are numerous laboratory tests that can be used to help include/exclude MS, but no definitive diagnosis can be based just on these investigative findings. In terms of MRI and CSF abnormalities, childhood MS appears to be similar to adult onset MS. MRI findings are positive in 80% of cases with multiple lesions found in the brainstem, cerebellum, and central white matter (most notably in the periventricular region) on T2 weighted images. CSF examination reveals abnormalities in more than 2/3 of children with tests showing an elevated total protein, an increase in gammaglobulin, and electrophoresis revealing IgG oligoclonal bands in 85% of cases. Pleocytosis is also seen (50-100 lymphocytes per cubic mm) with a tendency to be more markedly elevated in childhood MS (1). Visual, brainstem auditory, and somatosensory evoked potentials support clinical suspicion as well, by demonstrating the existence of multiple demyelinating lesions within the CNS. These neurophysiological tests have been found to be abnormal in 70%, 50%, and 75% of MS children respectively (1).
Because of the endless combination of signs and symptoms in MS, its slowly progressive nature, and the lack of definitive investigative testing, diagnosing MS in children is often difficult. In order to establish a criteria for MS in adults, the Poser Committee created the following categories that can be applied to childhood onset MS as well:
1. Clinically definite MS: 2 attacks plus clinical signs or investigative evidence of 2 lesions.
2. Laboratory supported definite MS: 2 attacks plus clinical signs or investigative evidence of 1 lesion. Abnormal CSF (oligoclonal bands) is also found.
3. Clinically probable MS: 2 attacks plus clinical signs or investigative evidence of 1 lesion.
4. Laboratory supported probable MS: 2 attacks plus abnormal CSF (oligoclonal bands).
This diagnostic criteria are particularly useful in diagnosing MS in children because other demyelinating diseases can appear clinically similar. The following are some of the more common demyelinating disorders of childhood: Schilder's Disease, childhood MS, Devic disease (neuromyelitis optica), acute disseminated encephalomyelitis, acute necrotizing encephalomyelitis, central pontine myelinolysis, Leber optic atrophy, acute hemorrhagic leukoencephalitis, adrenoleukodystrophy.
Other diseases that should be considered in the differential diagnosis of MS include diseases with similar presentations. Disseminated lupus is one disease that can also produce recurrent hemiplegia. There are many other disease processes that fit in this category including Behcet's disease, arteriovenous malformation, vitamin B12 deficiency, and Lyme disease.
Until recently, there were not many treatment options available for children with MS and while there has been recent advancements in therapeutic interventions, most of the information has been derived from adult onset MS. The bottom line is that there is no cure for MS. There are, however, treatments available to shorten the duration of an attack, lengthen remission, and alleviate the symptoms.
Symptomatic treatment may be needed for treating spasticity, neurogenic bladder, bowel symptoms, pain, fatigue, and seizures. As for shortening the duration of acute relapses, corticosteroids can be used. It should be noted, however, that while corticosteroids speed the recovery from an acute attack, the actual extent of recovery is unchanged and it does not prevent future relapses.
In order to reduce the frequency of attacks for patients with relapsing-remitting or secondary progressive course of MS, beta-interferon or daily subcutaneous administration of copolymer I may be beneficial. Interferons such as Beta IB and IA lessens the frequency of relapses by 1/3 by down-regulating antigen recognition. However, like corticosteroids, it has no effect on the extent of disability. Copolymer I, a synthetic polypeptide, has also shown similar results with both showing the ability to decrease active and new lesions as demonstrated on MRI.
The natural history of MS can be unpredictable. Some children have only one attack during their childhood with many years of remission. Others have multiple recurrences that occur within a few months. In order to aid in the determination of prognosis, it is important to understand that the clinical course of MS can be divided into 4 categories:
1. Relapsing/remitting MS: A clearly defined disease that relapses with either full recovery or with sequelae and residual deficit on recovery.
2. Secondary progressive MS: A disease that initially follows a relapsing/remitting course but becomes progressive.
3. Primary progressive MS: A disease that progresses from the onset with only temporary plateaus and relatively minor improvements.
4. Progressive-relapsing MS: A disease that progresses from onset with clear acute relapses.
The prognosis of childhood MS appears to be similar to adult onset MS in terms of the clinical course, rate of progression and rate of relapses. In general, childhood MS presents primarily as a relapsing-remitting course, with one study finding that 56% of children had a relapsing-remitting course, 22% with a primary progressive course, and 22% with a mixed course (2).
In summary, MS is a common demyelinating disease that should not be overlooked in children. The etiology has not been fully elucidated, nor has a cure been found. Identification of the disease, determining its clinical course, and providing the appropriate therapies currently available, appear to be the essential clinical steps thus far.
1. True/False: Childhood MS most commonly occurs in children between the age of 10-15 years.
2. The etiology of MS is probably related to: a. A dysfunction in autoimmune regulation b. Environmental factors c. Hereditary factors d. All of the above
3. True/False: Visual disturbances is one of the most common manifestations of childhood MS.
4. True/False: Laboratory investigations usually provide a definitive diagnosis for MS.
5. True/False: Corticosteroids can speed the recovery from an acute attack.
1. Menkes JH. Chapter 7 - Autoimmune and Postinfectious Diseases. In: Menkes JK. Textbook of Child Neurology, 5th Edition. 1995, Baltimore: William and Wilkins, pp. 528-534.
2. Kaye EM. Chapter 55 - Disorders Primarily Affecting White Matter. In: Swaiman KF, Ashwal S (eds). Pediatric Neurology Principles and Practice, 3rd Edition. 1999, St. Louis: Mosby, pp. 849-851.
3. Lott IT. Chapter 42 - Demyelinating Diseases of Childhood. In: Berg BO (ed). Principles of Child Neurology. 1996, New York: McGraw-Hill, pp. 953-956.
4. Lindsay KW, Bone I. Neurology and Neurosurgery Illustrated. 1997, Edinburgh: Churchill Livingstone.
5. Aminoff MJ. Chapter 24 - Nervous System. In: Tierney LM, McPhee SJ, Papadakis MA (eds). Current Medical Diagnosis and Treatment, 40th edition. 2001, New York: McGraw-Hill, pp. 1004-1006.
6. Cole GF, Stuart CA. A long perspective on childhood MS. Develop Med Child Neurol 1995;37:661-666.
7. Cole GF, Auchterlonie LA, Best PV. Very early onset Multiple Sclerosis. Develop Med Child Neurol 1995;37:667-672.
8. Sindern E, Haas J, Stark E, Wurster U. Early onset MS under the age of 16: clinical and paraclinical features. Acta Neurol Scand 1992;86:280-284.
Answers to questions
1.True, 2.d, 3.True, 4.False, 5.True