A 5-year-old male tripped and fell in his gym class at school while chasing a ball on October 8, 2013. He hit his head on bleachers. He did not lose consciousness, but was reportedly dazed when he saw the school nurse. No formal diagnostic work-up or treatment was initiated at that time. On October 15, his mother noticed that he suddenly looked tired, that the right side of his face was drooped, that he staggered when he walked and that he had difficulty responding verbally to her. He was taken promptly to a hospital on October 16. A MRI/MRA of the brain revealed a left thalamic stroke (see Figure 1). A C-spine MRI showed C1-C2 and C4-C5 ligamentous injury for which he was placed in a cervical collar for 6 weeks. He was admitted to an inpatient rehabilitation unit on October 22.Figure 1: Magnetic resonance angiogram (MRA) of brain demonstrating left thalamic stroke.
Discussion: The cause of this child’s sudden stroke was vertebral artery dissection (VAD). Stroke as a consequence of VAD has been only infrequently reported in children. In a significant percentage of cases, a temporal relationship between trivial neck or head trauma and the subsequent development of VAD has been identified. There is typically a history of neck hyperextension with torsion. In the review of VAD in children by Couldwell and associates, the majority of children presented with a combination of signs and symptoms, including eye signs or symptoms (72%), paresis/paralysis of 1 or more extremities (54%), ataxia (53%), headache (38%), and vomiting (34%). Interestingly, neck pain, a hallmark symptom of VAD in adults, was noted in only 12% of these children with VAD.
Angiography was the most common imaging study (93%) used to diagnose the VAD in these patients. Noninvasive imaging studies, such as brain MRI with magnetic resonance angiography (MRA) and cranial CT with computed tomography angiography (CTA), have supplanted conventional angiography in the diagnosis of cervicocephalic dissection. Conventional angiography, however, is used in younger patients when clinical suspicion of arterial dissection is high despite negative findings on the noninvasive studies. In the Couldwell study, boys outnumbered girls by a ratio of 6.6:1. In contrast, in the adult population the ratio is 1.3:1.
Arterial dissection occurs when the arterial walls are separated by hemorrhage. This creates a false lumen in the space where blood seeps into the vessel wall, causing a change in blood flow turbulence resulting in thrombotic stenosis or occlusion at the site of injury. This results in ischemic stroke(s) and associated neurologic sequelae. Although cerebral ischemia can be due to hypoperfusion, it is most commonly the result of thromboembolism. Prognosis is dependent on the clinical status at presentation, the degree of subsequent recanalization, and the time to onset of treatment.
Early initiation of treatment results in more successful thrombolytic reversal of thrombotic occlusions. Intravenous fibrinolytic therapy within the first 3 hours of an ischemic stroke onset has more favorable outcomes, while treatment after 4.5 hours has demonstrated no net benefit. Subsequent treatment of VAD after the acute phase is controversial but includes antiplatelet or anticoagulation therapy.
Children who have a stroke secondary to a vertebral artery dissection may develop significant focal neurologic deficits. This child’s most prominent residual deficits included motor incoordination,right sided weakness, right hemisensory impairment, and expressive language deficits. He showed significant functional improvement in response to comprehensive inpatient rehabilitation therapies, which included exercises and activities to improve his gait, strength, endurance, balance, coordination, dexterity, and communication skills. He is expected to show continuing incremental improvement with ongoing rehabilitation therapy in the outpatient clinic setting, but he remains at risk for lasting neurocognitive deficits and behavioral dysfunction. He was directed to avoid contact sports and high-speed amusement park rides. His Lovenox was discontinued following his inpatient rehabilitation course, and he was instituted on aspirin 81 mg daily for secondary stroke prevention, which he will remain on for at least 2 years following his initial presentation. He will undergo a brain MRI and a head and neck MRA at 2 years following his stroke.
It is postulated that the incidence of VAD in children is likely underestimated and inadequately recognized. VAD should be included in the differential diagnosis of ischemic strokes in children, particularly when the child has experienced preceding head or neck trauma, even if seemingly trivial.
Hasan I, Wapnick S, Tenner MS, Couldwell W. Vertebral artery dissection in children: a comprehensive review. Pediatr Neurosurg. 2002;37(4):168-677.
An 11-year-old female from Liberia was recently adopted by a family in the United States and brought to CHOP for an overall health evaluation. In preparation for the adoption, she underwent medical testing and was found to be HIV negative and hepatitis A, B, and C negative. She had no known history of cardiac or pulmonary problems. However, she presented with a history of progressive loss of bowel and bladder function, progressive paraparesis of her lower extremities, and cervicothoracic kyphosis. Scoliosis X-rays showed extensive calcific lymphadenopathy of the mediastinum, hilum, retroperitoneum, and pericardium. A spinal MRI (see Figure 2) noted severe destruction of multiple vertebral bodies from T1- 6, compression deformity of T7, mild compression deformities of T8-11, and osseous/disc irregularities from L4-S2. After it was determined her progressive paraplegia and spinal deformity were the result of spinal tuberculosis, she was admitted to the inpatient rehabilitation unit for comprehensive therapies and ongoing medical management.
Discussion: Figure 2: MRI images showing significant acute kyphosis leading to severe spinal cord compression at T6 level.Identified in Egyptian mummies from around 3400 BC, spinal tuberculosis (TB) is one of the oldest recorded diseases. Primarily affecting children and young adults in endemic countries, and adults in developed Western and Middle Eastern countries, its exact incidence and prevalence are unknown. Spinal TB is also known as “Pott’s spine” or “Pott’s disease.” As described by Sir Percival Pott in 1779, it is characterized by destruction of the disk space and surrounding vertebral bodies, as well as progressive kyphosis. Clinical features of spinal TB include focal pain, stiffness, and spasm of back muscles. Other potential clinical manifestations include a cold abscess, a gibbus deformity of the spine, and focal neurological deficits, including sensory loss, motor weakness, spasticity, and incoordination, as well as urinary and bowel incontinence.
Although most commonly affecting the thoracic region, spinal TB can be found at any level of the spinal cord, which determines its neurological manifestations. Patients with cervical lesions may present with symptoms of weakness, pain, and numbness of both upper and lower extremities, which can progress to tetraplegia. Patients with thoracic or lumbar lesions retain upper extremity function but may develop lower extremity deficits that may progress to paraplegia.
Spinal TB is caused by the invasion of vertebral bodies by Mycobacterium tuberculosis from a primary infection site, typically from a lung or kidney lesion. In patients with extrapulmonary TB, an estimated 10% will have skeletal involvement, of which spinal TB accounts for almost 50%. Spinal TB can be confirmed by identifying acid-fast bacilli on microscopy or culture, or by polymerase chain reaction (PCR) testing. Currently the gold standard for early histopathological diagnosis is needle biopsy of the affected site by neuroimaging. Unfortunately, biopsies may yield false-negative results. Thus, the diagnosis of spinal TB may be made on the basis of clinical manifestations and imaging studies when bacteriological studies are negative.
Spinal X-rays tend to remain normal until advanced stages of the disease. Computed topography (CT) of the spine is typically favored because it can more readily identify osseous abnormalities of the spine. MRI of the spine, however, remains the best choice for neuroimaging because it identifies both osseous and neurological involvement. It is advisable to screen the entire vertebral column to identify possible noncontiguous vertebral lesions.
Although the exact treatment protocol for spinal TB remains controversial, most patients (82% to 95%) respond favorably to medical management. Surgery may be performed in selected cases, including patients with pan-vertebral lesions, those with severe thoracic kyphosis, and patients with evidence of progressive clinical deterioration. Spinal TB has a relatively good prognosis if treated appropriately in a timely manner.
Intensive and comprehensive inpatient rehabilitation, including physical and occupational therapy, as well as the judicious prescription of appropriate orthotics and assistive devices, can potentially enable a patient with significant, functionally limiting neurologic deficits to achieve improved independence in his or her daily activities. Prompt referral to a physical medicine and rehabilitation specialist and early referral for comprehensive inpatient rehabilitation services may facilitate functional recovery and minimize or avoid potential complications, such as disuse atrophy, respiratory insufficiency, deep vein thromboses, systemic emboli, progressive joint contractures, spasticity, autonomic dysreflexia, functionally limiting neuropathic or musculoskeletal pain, postoperative pain, neurogenic bladder, neurogenic bowel, pressure ulcers, and heterotopic ossification.
While at CHOP, our patient underwent a posterior spinal fusion with instrumentation from C6 to L1 with a partial vertebral corpectomy and a spinal cord decompression from T3 to T6. She was then admitted to inpatient rehabilitation for 42 days, where she received occupational, physical, and speech therapies in addition to cognitive group therapy and psychology support. On weekdays she received an average of 6 hours of therapies per day, 3 hours per day on weekends. She was also prescribed bilateral hip-knee-ankle-foot orthotics (HKAFOs), multi-podus boots, and knee immobilizers. She has been discharged home and receives outpatient physical and occupational therapies. Although primarily wheelchair bound, she currently ambulates short distances using a rolling walker with minimum assistance.
Garg, RK, Somvanshi, DS. Spinal tuberculosis: a review. J Spinal Cord Med. 2011;34:440-454.
A previously healthy 7-year-old male presented with a 6-day history of fever, right upper quadrant abdominal pain, vomiting, and jaundice. Initial lab findings revealed: white blood cell count 15.6, hemoglobin 11, platelet 97, sodium 125, hyperbilirubinemia, elevated liver enzymes, and coagulopathy. A CT scan of the abdomen noted ascites, diffuse lymphadenopathy, and hepatosplenomegaly. An abdominal ultrasound revealed a mass near the porta hepatis and splenomegaly.
Further evaluation within the first days of his hospitalization revealed his ferritin was elevated to 10 000 and his soluble IL-2 receptor was elevated to 22 000. His physical exam was significant for splenomegaly and lymphadenopathy. A bone marrow biopsy showed a slightly hypocellular marrow with trilineage hematopoiesis but no evidence of any hemophagocytosis or blasts. He was positive for the SAP gene mutation. He also presented with an EBV viremia/ encephalitis and hepatitis. His hospital course prior to admission to The Children’s Hospital of Philadelphia was complicated by candida parapsilosis fungemia and seizures with an acute decline in mental status. He was diagnosed with X-linked lymphoproliferative syndrome and secondary hemophagocytic lymphohistiocytosis related to an EBV infection and admitted to inpatient rehabilitation due to severe deconditioning and severe cognitive and language deficits. During his hospitalization, the child received physical, occupational, and speech therapies 7 times per week. He also participated in cognitive group therapy 5 times per week with a special education teacher.
Discussion: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of the immune system in which there is excessive T-cell activation and inflammatory cytokine production, resulting in progressive multiorgan failure if untreated. HLH is not a malignancy; it is a syndrome of excessive inflammation and tissue destruction due to an abnormal immune activation. Prompt and accurate diagnosis and timely treatment are critical.
HLH represents a spectrum of inherited and acquired conditions characterized by disturbed immune regulation. Primary or familial hemophagocytic lymphohistiocytosis (FHL) is a heterogeneous autosomal recessive genetic disorder seen primarily in infancy and early childhood. Secondary hemophagocytic lymphohistiocytosis is often diagnosed in older patients (children and adults), those with no family history associated with this form of disease, and for whom a clear trigger of the HLH episode has been identified. In practice, distinction between primary and secondary HLH is not essential for initial diagnosis and management. However, identification of a gene mutation is useful for subsequent medical management. Genetic information can be helpful in determining the likelihood of reoccurrence, the need for hematopoietic cell transplant, and the risk of HLH in family members.
Several aspects of the clinical presentation of HLH contribute to delayed diagnosis, including the rarity of the syndrome, the variable clinical presentation, and the lack of specificity of the clinical and laboratory findings. Initial signs and symptoms of HLH can mimic common infections, fever of unknown origin, hepatitis, or encephalopathy. With few exceptions, the clinical features are similar regardless of whether an underlying genetic defect is identified. A set of diagnostic criteria was recommended by the HLH-2004 research protocol (revised in 2007). This includes diagnosis of a specific gene defect and/or presence of at least 5 of the following 8 criteria:
Often a diagnosis of HLH is made for a patient who only partially meets criteria because definitive HLH therapy must be initiated when there is inadequate response to general supportive care and because of the high mortality rate of HLH in the absence of appropriate treatment. For all patients with suspected HLH, urgent referral to a hematology or oncology specialist is required.
The goal of HLH treatment is to suppress life-threatening inflammation by suppressing immune response. This can include a combination of chemotherapy, immunotherapy, and steroids. Antibiotics and antiviral drugs may also be used. These treatments may be followed by a bone-marrow or stem-cell transplant in patients with persistent or recurring HLH or those with an HLH gene mutation and/or central nervous system disease.
The severe deconditioning and muscle atrophy associated with this disorder typically results in significant impairment in a child’s functional status and compromises his or her ability to resume play and school activities. Inpatient rehabilitation and subsequent outpatient therapies, as well as the prescription of appropriate orthotic devices and assistive equipment, can be critical in facilitation of a child’s return to functional independence in daily activities at home and in the community.
This child made significant gains in strength, endurance, cognition, balance, motor planning, and coordination during his stay in rehabilitation. He is currently functioning close to baseline level of independence. The child was discharged with continued outpatient physical, occupational, and speech therapies.
Jordan, MB, Allen, CE, Weitzman, S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15); 4041-4052.
McClain, KL (2013). Treatment and prognosis of hemophagocytic lymphohistiocytosis. UpToDate.com. Available at: http://bit.ly/HLHtreat. Accessed January 30, 2014.
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