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Among syndromes related to genetic inborn errors of metabolism, mitochondrial encephalopathies are the most frequent affecting the brainstem. Mitochondrial diseases include a wide range of clinical syndromes associated with deficits of the oxidative phosphorylation, caused by partial or complete deficits of one or more enzymatic complexes of the respiratory chain[ 12 ].

Hereditary transmission may be autosomal recessive, autosomal dominant, online dating cosimo grasso , X-linked or maternal[ 13 ]. The defect of the online dating cosimo grasso respiratory chain may, in fact, online dating cosimo grasso , be caused by genetic mutations of either nuclear DNA or mitochondrial DNA[ 14 - 17 ].

Metabolic vulnerability is an important issue for the involvement of the brainstem in these diseases[ 18 ]: In fact, cells and tissues with high metabolic demand are more susceptible to specifically incur damage due to their inability or incomplete ability to reduce oxygen and finally produce ATP energy molecules[ 19 ].

The clinical presentation of these diseases is multi-systemic because different tissues and organs are involved. The diagnosis is challenging due to the extreme genetic and phenotypic heterogeneity, online dating cosimo grasso. Due to their pathogenesis, the brainstem lesions are symmetrical, sometimes confined to the same specific location bilaterally. The substantia nigra, mainly the online dating cosimo grasso reticulata, the medullary and pontine tegmentum and the inferior colliculi are reported as the most frequent sites[ 20 ].

The inferior olivary nuclei are often involved, although this is not seen in children who die before 1 year of age[ 20 ]. The loss of Purkinje cells and cerebellar involvement is, in fact, more characteristic of other mitochondrial encephalopathies such as myoclonic epilepsy with ragged-red fibers MERRFmitochondrial encephalopathy, lactic acidosis and stroke-like episodes MELAS online dating cosimo grasso Kearns-Sayre syndrome[ 23 ].

However, differential diagnosis may be challenging because brainstem lesions have been described in these other mitochondrial disease, such as the involvement of the periacqueduttal gray matter and the superior cerebellar peduncles in MERRF[ 24 ], the bilateral medullary tegmentum in Kearns-Sayre syndrome[ 25 ] or brainstem infarct-like lesions that do not respect vascular territories in MELAS[ 26 ].

One recently identified multisystem mitochondrial disease with specific involvement of specific white matter tracts is the Leukoencephalopathy with Brainstem and Spinal cord involvement and Lactate elevation online dating cosimo grasso is consequent to mutations in the DARS2 gene encoding the mitochondrial aspartyl-tRNA synthetase[ ].

In this syndrome, the MRI pattern of bilateral and symmetric involvement of white matter of medial lemniscus and pyramids, dorsal columns, superior and inferior cerebellar peduncles, cerebellar white matter, associated with elevated lactate in magnetic resonance spectroscopy is specific, diagnostic and helpful for genetic characterization[ 28 ].

Among metabolic syndromes involving the brainstem, the central pontine myelinolysis, is the MRI feature of the osmotic demyelination syndrome, a metabolic syndrome occurring in patients who experience severe alterations of plasma osmolality or receive rapid correction of hyponatremia[ 29 ]. The T2 hyperintensity specifically involves the central pons with signal changes related to alteration of the integrity of the myelin sheaths but not of the axons.

The signal alteration may extend cranially to the midbrain and laterally to the middle cerebellar peduncles[ 29 ]. When extra-pontine myelinolisis is associated, online dating cosimo grasso , bilateral and symmetric T2 hyperintensity of the basal ganglia is observed[ 22 ], online dating cosimo grasso. This condition is transient and, if the correct steady state of osmolality is established, the lesion tends to completely resolve.

Despite the underlying mechanisms of this condition are still under debate and investigation, online dating cosimo grasso , the MRI alterations are greatest at 3 to 6 mo after the beginning of treatment and reversible in nature[ 30 ] Figure 8.

The terms rhombo-encephalitis and brainstem encephalitis are interchangeably used and referred to the involvement of infra-tentorial structures brainstem and cerebellum in the former and brainstem only in the latter in the context of an inflammatory disease, either infectious, autoimmune or paraneoplastic. The most frequent agents associated with involvement of the brainstem are Listeria monocytogenes and enterovirus 71, followed by herpes simplex viruses[ 32 ]. MRI findings in these pathological conditions are not specific; lesions are usually multiple, patchy and asymmetric hyperintense on T2 weighted images and are not typically associated with T1 contrast enhancement Figure 9.

Selective vulnerability of the substantia nigra has been shown for some specific viral encephalitides St. Louis encephalitis and Japanese encephalitis [ ]. Patchy enhancement and abscess formation with ring enhancement after contrast agent injection can be observed at all levels of the brainstem in Listeria monocytogenes infection[ 35 ] and in the miliary pattern of tuberculosis[ 36 ] due to the formation of abscesses Figure Abscesses are mainly located at the pons online dating cosimo grasso show a faint T2 hyperintensity due to vasogenic edema.

The central portion of the lesions may be iso- or hyperintense on T2 weighted images[ 37 ]. In the case of tuberculomas, the signal of the central portion is hypointense on T2 weighted images[ 38 ]. Due to the hematogenous spread, abscesses usually show a distribution resembling the arterial embolic strokes. When there is a clinical suspicion of infection, diagnosis may be reached by measuring the levels of antibodies, by blood and CSF culture tests.

For viral encephalitides, polymerase chain reaction allows to demonstrate the presence of viral DNA in the CSF. Brainstem lesions in the course of encephalitis may be associated with supra-tentorial alterations, in some cases with specific symmetric and bilateral involvement of the basal ganglia[ 22 ] Figure 9. After the demonstration of the pathogenetic role of immunoglobulin G anti-ganglioside GQ1b antibodies, patients with a clinical presentation ranging from ophtalmoplegia and ataxia to altered consciousness and areflexia, previously described as Miller-Fisher syndrome or Bickerstaff encephalitis or Guillan-Barrè syndrome were classified as affected of an unique anti-GQ1b antibody syndrome[ 40 - 42 ], with variable central and peripheral nervous system involvement.

In these syndromes, immune cross-reaction seems to be triggered by previous exposure to Campylobacter jejuni[ 42 ] and Mycoplasma pneumoniae[ 43 ]. Bickerstaff encephalitis may mimic a glioma: Metabolic profile at MR spectroscopy, MRI re-evaluation after corticosteroid treatment and CSF levels of anti-GQ1b autoantibodies guide the differential diagnosis Figure After common viral infections such as influenza A, influenza B, parainfluenza II, human herpes virus 6, coxsackie virus or enterovirus, a rapidly progressive encephalopathy known as acute necrotizing encephalopathy ANE may occur in otherwise healthy children[ 44 ].

Both familiar and sporadic forms have developed in patients harboring missense mutations of the nuclear pore gene Ran-binding 2[ 45 ] Figure ANE is considered different from Acute Disseminated Encephalomyelitis ADEM.

ADEM is, in most of the cases, a monophasic and multifocal inflammatory disease that has a typical temporal relationship with an infection or a vaccination occurred 1 to 3 wk before the clinical onset[ ].

Brainstem lesions have a MR appearance indistinguishable from online dating cosimo grasso of multiple sclerosis lesions; however, in patients with ADEM there is a higher frequency of midbrain lesions and lesions are more symmetrical and bilateral than in patients with multiple sclerosis[ 48 ].

The bilateral and symmetrical involvement of cerebellum, basal ganglia and thalami and relative sparing of corpus callosum supports the diagnosis of ADEM Figure The brainstem is frequently involved in patients with multiple sclerosis and lesions have frequently a clinical correlate because of the scarce functional resilience of fiber tracts and gray matter nuclei in the brainstem[ 50 ], online dating cosimo grasso. MS lesions in the brainstem are more prevalent at the floor of the fourth ventricle and in the periphery of the brainstem, especially the pons[ 51 ] Figure The infratentorial site is considered specific for the diagnosis of multiple sclerosis, being one of the four sites necessary and or sufficient for the dissemination in space criteria revised McDonald criteria [ 52 ].

The incidence of multiple sclerosis peaks at years and is rare in children[ 49 ]. Among demyelinating diseases, it must be mentioned that brainstem involvement including the medullary area postrema may be observed in Neuromyelitis Optica spectrum disorders, both with or without serum aquaporin-4 immunoglobulin G autoantibodies[ 56 ], online dating cosimo grasso.

A rare autosomal-recessive neurodegenerative disorder caused by a combined deficiency of molybdenum-dependent enzymes is the Molybdenum cofactor deficiency. This condition is considered rare in prevalence but probably under-reported. This deficiency leads to an early-onset encephalopathy or to an atypical late onset syndrome with global developmental delay. Share your videos with friends, family, and the world View the profiles of people named Cosimo Grasso.

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