Early-Onset Shapiro Syndrome Variant Treated with Pizotifen: A Case Report

Abstract

Shapiro Syndrome is a rare entity defined by the triad of recurrent spontaneous hypothermia, hyperhidrosis, and agenesis of the corpus callosum. Fewer than 100 cases have been reported so far and there are only few cases without a complete agenesis of corpus callosum ("Shapiro Syndrome Variant"). In this article, we report the clinical, electroencephalographic, and neuroimaging data of a patient with early-onset Shapiro Syndrome Variant. The case study describes a 4-year-old patient with episodes characterized by generalized hyperhidrosis, hypotonia, impaired consciousness, and hypothermia with onset before the first year of age. We captured an event during which the EEG showed rhythmic low- to medium-voltage theta waves without clear epileptiform activity. Brain MRI was normal and Shapiro Syndrome Variant was hypothesized. We started treatment with pizotifen, and after 2 years, the patient showed a reduction in frequency and duration of episodes. Shapiro Syndrome, although rare, should be considered in the differential diagnosis in patients with neurovegetative symptoms which suggest epileptic attacks at first. Our case is of particular interest to specialists because Shapiro SyndromeVariant is a rare syndrome and our patient had a very early onset of symptoms.In addition, we report our experience with pizotifen therapy, which produced a good response.

Atypical Case of Early-Onset Shapiro Syndrome: Diagnostic Approach and Therapeutic Challenges

“…11 In his original publication, Shapiro et al attributed these signs to dysregulation of encephalic pathways secondary to CCA; however, since the syndrome was originally described, 19 patients have been reported with an intact corpus callosum but presenting clinical findings compatible with SS. [2][3][4][5][6][7][8][9][10][11] Since the variant was accepted into the spectrum of SS, rationales attributing the clinical manifestations to a structural cause have been disputed. Newer theories have been proposed for its physiopathology; some authors suggest that a basal forebrain malformation could produce a disconnection of the cortico-hypothalamic and hippocampo-hypothalamic networks, as well as the loss of the afferent nerve fibers from the septum to the hypothalamus, which could result in a dysregulation of the autonomic system.…”

“…11 In his original publication, Shapiro et al attributed these signs to dysregulation of encephalic pathways secondary to CCA; however, since the syndrome was originally described, 19 patients have been reported with an intact corpus callosum but presenting clinical findings compatible with SS. 2 3 4 5 6 7 8 9 10 11…”

“…Cases without CCA have also been described, considering it a variant of the condition. [2][3][4][5][6][7][8][9][10][11] Among findings, it has been described that paroxysmal hypothermia is present in all the patients with typical and variant SS (100%), hyperhidrosis may be present in up to 92.3% of the cases, while CCA is reported in only 15.4% of cases. 11 Other frequently reported findings reported include pallor, altered consciousness (i.e., somnolence, lethargy, and obtundation), sleep disorders, chills, weakness, and bradycardia.…”

“…Cases without CCA have also been described, considering it a variant of the condition. 2 3 4 5 6 7 8 9 10 11…”

A new perspective of hypothalamic disease: Shapiro's syndrome

“…Initially, William Shapiro et al (1) considered the syndrome to be "diencephalic epilepsy, " but this hypothesis was contradicted by the variant form of SS and the nonepileptiform focal changes of the EEG (17,23). At present, there are three hypotheses, which are hypothalamic dysfunction, neurotransmitter dysfunction (2,5,9,20,27), and endogenous hypermelatonemia (6).…”