Duarte Salgado

Late Cerebrovascular Complications After Radiotherapy for Childhood Primary Central Nervous System Tumors.

BACKGROUND Brain radiotherapy plays a central role in the treatment of certain types of childhood primary central nervous system tumors. However, damage to surrounding normal brain tissue causes different acute and chronic medical and neurological complications. Despite the expected increase in number of childhood primary central nervous system tumor survivors, studies assessing the occurrence of late cerebrovascular complications, such as cavernoma, moyamoya, microbleeds, superficial siderosis, and stroke are sparse. METHODS We undertook a retrospective consecutive case series review describing the occurrence and characteristics of late cerebrovascular complications in 100 survivors of childhood primary central nervous system tumors treated with radiotherapy. Demographic, clinical, and radiological findings including gradient echo brain magnetic resonance data were retrieved. RESULTS Late cerebrovascular complications were found in 36 (36%) of the patients included in the study. Mean age at radiotherapy was 8.6 years (3-17) and at diagnosis was 23.9 years (3-38). The majority were males (21; 58%). The most common complications were microbleeds (29/36; 80.6%) and cavernomas 19 (52.8%). In seven (19.4%), late cerebrovascular complications were symptomatic: epilepsy (two), motor and language deficit (two), and sensorineural hearing loss and progressive ataxia (three) associated with cavernomas, stroke, and superficial siderosis, respectively. Follow-up length was associated with an increased diagnosis of late cerebrovascular complications (P < 0.0001). Late cerebrovascular complications occurred more commonly in children treated with whole-brain radiation therapy (P = 0.046). Factors such as sex, chemotherapy, and histological type of tumor were not correlated with the occurrence of late cerebrovascular complications. CONCLUSION Although not usually symptomatic, late cerebrovascular complications occur frequently in survivors of childhood primary central nervous system tumors treated with radiotherapy. Prolonged follow-up increases the probability of diagnosis. The impact and prognostic value of these late cerebrovascular complications is yet to be clarified.

Microbleeds and cavernomas after radiotherapy for paediatric primary brain tumours

BACKGROUND With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST. OBJECTIVE To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location. METHODS Retrospective cohort study of 190 paediatric patients being followed for PCNST in a single referral oncological centre. The frequency of FHD lesions was compared between paediatric PCNST treated (n=132) and not treated (n=58) with brain radiation. Microbleed Anatomical Rating Scale (MARS) was used for systematic identification of these cerebrovascular lesions and to address the consistency between the topographic location of each lesion and the location of the focal radiotherapy area. Univariate analysis to address the role of variables such as tumour histology, location, gender and age of children at the beginning of radiotherapy, duration of follow-up and chemotherapy was performed. RESULTS FHD lesions (microbleeds and cavernomas) occurred exclusively and in a high percentage (41.6%) in PCNST survivors treated with brain radiation. Younger age at the diagnosis (p=0.031), duration of follow-up (p=0.010) and embryonal histology (p=0.003) positively correlated with the occurrence FHD lesions. FHD lesions were topographically concordant with the brain focal irradiation area in 3/19 (15.8%) patients from the focal RT subgroup and in 22/111 (19.8%) patients from the WBRT plus focal RT subgroup. CONCLUSION Our study, which is one of the largest to date on the topic, shows that FHD lesions are a common complication after radiotherapy for childhood PCNST. The young brain is probably more susceptible to radiation-induced late cerebrovascular injury. Diffuse small vessel disease and ceiling effect may account for the low topographic concordance we found. The clinical implications of FHD lesions in this specific population are yet to be clarified.

Three Decades of Drift: The Misdiagnosis of Predominantly Neuropsychiatric Multiple Sclerosis

To the Editor: Neuropsychiatric disturbances, such as behavior, mood, and personality changes, are often recognized during multiple sclerosis (MS) evolution. Psychiatric presentation and dominant cognitive MS is very rarely reported, and occurs in less than 1% of cases. In this report, we describe a case of MS with predominant cognitive and psychiatric manifestations from the beginning, misdiagnosed as a pure psychiatric disorder for more than three decades. Case Report An African 52-year-old-woman, diagnosed and treated as having histrionic personality disorder and depression for 32 years, was sent for neurological consultation because of subacute gait disturbance. Neurological examination disclosed lower limb asymmetric ataxia, left-side hemihypoesthesia, and spasticity. Brain magnetic resonance showed lesions suggestive of MS (Figure 1). Oligoclonal bands were positive in the cerebrospinal fluid and visual evoked potential showed decreased latency in right eye. Review of hermedical charts disclosed the presence of episodes of transient sensory and visual neurological symptoms (Figure 2). Depression and histrionic behavior appeared concomitantly with the first neurological symptoms, at the age of 21, and the subsequent episodes were followed by marked aggravation of the histrionic behavior. No objective or congruent findings on clinical examination and complementary exams (brain X-ray, brain CT, electromyography) were found or evaluated. With irregular adherence, she was receiving psychotherapy, and taking chlordiazepoxide and amitriptyline. Despite being evaluated on three occasions by neurologists and on one by an ophthalmologist, the diagnosis remained unchanged. She had progressive cognitive decline and manifested persistent histrionic behavior interfering with her professional activities during these 32 years of disease. The patient was diagnosed with MS. After starting interferon b21a, she had two new attacks, one sensory and another motor. No changes were noted in psychiatric and cognitive status.