These data support accumulating evidence that CMI is a disorder of the para-axial mesoderm that is characterized by underdevelopment of the posterior cranial fossa and overcrowding of the normally developed hindbrain. Tonsillar herniation of less than 5 mm does not exclude the diagnosis. Clinical manifestations of CMI seem to be related to cerebrospinal fluid disturbances (which are responsible for headaches, pseudotumor-like episodes, endolymphatic hydrops, syringomyelia, and hydrocephalus) and direct compression of nervous tissue. The demonstration of familial aggregation suggests a genetic component of transmission.

BackgroundThe pathogenesis of Chiari malformations is incompletely understood. We tested the hypothesis that different etiologies have different mechanisms of cerebellar tonsil herniation (CTH), as revealed by posterior cranial fossa (PCF) morphology.MethodsIn 741 patients with Chiari malformation type I (CM-I) and 11 patients with Chiari malformation type II (CM-II), the size of the occipital enchondrium and volume of the PCF (PCFV) were measured on reconstructed 2D-CT and MR images of the skull. Measurements were compared with those in 80 age- and sex-matched healthy control individuals, and the results were correlated with clinical findings.ResultsSignificant reductions of PCF size and volume were present in 388 patients with classical CM-I, 11 patients with CM-II, and five patients with CM-I and craniosynostosis. Occipital bone size and PCFV were normal in 225 patients with CM-I and occipitoatlantoaxial joint instability, 55 patients with CM-I and tethered cord syndrome (TCS), 30 patients with CM-I and intracranial mass lesions, and 28 patients with CM-I and lumboperitoneal shunts. Ten patients had miscellaneous etiologies. The size and area of the foramen magnum were significantly smaller in patients with classical CM-I and CM-I occurring with craniosynostosis and significantly larger in patients with CM-II and CM-I occurring with TCS.ConclusionsImportant clues concerning the pathogenesis of CTH were provided by morphometric measurements of the PCF. When these assessments were correlated with etiological factors, the following causal mechanisms were suggested: (1) cranial constriction; (2) cranial settling; (3) spinal cord tethering; (4) intracranial hypertension; and (5) intraspinal hypotension.

Objective The pathogenesis of CM-I is incompletely understood. We describe an association of CM-I and TCS that occurs in a subset of patients with normal size of the PCF. Methods The prevalence of TCS was determined in a consecutively accrued cohort of 2987 patients with CM-I and 289 patients with low-lying cerebellar tonsils (LLCT). Findings in 74 children and 244 adults undergoing SFT were reviewed retrospectively. Posterior cranial fossa size and volume were measured using reconstructed 2D computed tomographic scans and MR images. Results were compared to those in 155 age- and sex-matched healthy control individuals and 280 patients with generic CM-I. The relationships of neural and osseus structures at the CCJ and TLJ were investigated morphometrically on MR images. Intraoperative CDU was used to measure anatomical structures and CSF flow in the lumbar theca. Results Tethered cord syndrome was present in 408 patients with CM-I (14%) and 182 patients with LLCT (63%). In 318 patients undergoing SFT, there were no significant differences in the size or volume of the PCF as compared to healthy control individuals. Morphometric measurements demonstrated elongation of the brain stem (mean, 8.3 mm; P < .001), downward displacement of the medulla (mean, 4.6 mm; P < .001), and normal position of the CMD except in very young patients. Compared to patients with generic CM-I, the FM was significantly enlarged (P < .001). The FT was typically thin and taut (mean transverse diameter, 0.8 mm). After SFT, the cut ends of the FT distracted widely (mean, 41.7 mm) and CSF flow in the lumbar theca increased from a mean of 0.7 cm/s to a mean of 3.7 cm/s (P < .001). Symptoms were improved or resolved in 69 children (93%) and 203 adults (83%) and unchanged in 5 children (7%) and 39 adults (16%) and, worse, in 2 adults (1%) over a follow-up period of 6 to 27 months (mean, 16.1 months ± 4.6 SD). Magnetic resonance imaging 1 to 18 months after surgery (mean, 5.7 months ± 3.8 SD) revealed upward migration of the CMD (mean, 5.1 mm, P < .001), ascent of the cerebellar tonsils (mean, 3.8 mm, P < .001), reduction of brain stem length (mean, 3.9 mm, P < .001), and improvement of scoliosis or syringomyelia in some cases. Conclusions Chiari malformation type I/TCS appears to be a unique clinical entity that occurs as a continuum with LLCT/TCS and is distinguished from generic CM-I by enlargement of the FM and the absence of a small PCF. Distinctive features include elongation and downward displacement of the hindbrain, normal position of the CMD, tight FT, and reduced CSF flow in the lumbar theca. There is preliminary evidence that SFT can reverse moderate degrees of tonsillar ectopia and is appropriate treatment for cerebellar ptosis after Chiari surgery in this cohort.

The presence of antibodies to human T-cell lymphoma/leukemia virus Type I (HTLV-I) has been associated with chronic progressive myelopathy. We attempted to isolate the virus from the blood and spinal fluid of patients with chronic progressive myelopathy and to define the clinical, radiologic, and electrophysiologic features of this disease. Ten of 13 patients from tropical countries and 2 of 8 from the United States had serum antibodies to HTLV-I. The virus was detected in cultures of peripheral-blood lymphocytes from three of seven patients by means of Southern blot hybridization. Using a sensitive in vitro enzymatic gene-amplification technique, we detected HTLV-I sequences in fresh peripheral-blood mononuclear cells of all of 11 patients tested who were positive for the antibody, and in cell cultures of the spinal fluid from 3 of the 11 tested. Magnetic resonance imaging of the cranium revealed periventricular lesions in the white matter of 3 of the 12 antibody-positive patients. Five of these patients had mild axonal sensorimotor polyneuropathy, and one had bilateral lumbar radiculopathy. Visual evoked potentials were abnormal in three seropositive patients, and brain-stem evoked responses were abnormal in two. The detection of the DNA and proteins of HTLV-I strengthens the proposition that this virus is involved in the pathogenesis of a subset of cases of chronic progressive myelopathy.

The L689I mutation has similar effects to the T704M mutation and causes hyperKPP in this family. Because both of these hyperKPP mutations cause episodic muscle weakness, and because patients harboring another mutation (I693T) also can have episodic weakness, it is hypothesized that mutations occurring in this region of the sodium channel may cause episodic weakness through an impaired slow inactivation process coupled with enhanced activation.