Neurospectroscopy

Case Report 1: Absence of N-Acetylaspartate in the Human Brain.

N-acetylaspartate (NAA) contributes to the most prominent signal in proton magnetic resonance spectroscopy of the adult human brain. We report the absence of NAA in the brain of a 3-year-old child with neurodevelopmental retardation and moderately delayed myelination. Since normal concentration of NAA in body fluids is hardly detectable, 1H-MRS is a noninvasive technique for identifying neurometabolic diseases with absent NAA. This report puts NAA as a neuronal marker to question.

Methods

• MR: 2T scanner , 1H-MRS
• Subjects: 3-year-old child with neurodevelopmental retardation.

(a) An age-matched normal proton spectrum from the occipital gray matter with the prominent N-acetylaspartate (NAA) resonance at 2.02 ppm. (b–e) Complete absence of NAA in the spectra from different brain regions of the patient at age 3 years and 6 months. (b) Occipital gray matter. (c) Parieto-occipital white matter. (d) Basal ganglia. The absence of NAA becomes even more obvious in the long–echo time spectrum. (e) Parieto-occipital white matter at TE = 270 msec. At 3.75 ppm the unusual resonance is indicated.

Collaborations

Prof. Eugen Boltshauser, Department of Neurology, University Children’s Hospital Zurich

Contact

Ernst Martin
Ernst.Martinkispi.uzh.ch

Case Report 2: Creatine Deficiency and Guanidinoacetyl-phosphate Accumulation in the Brain of two Adult Sisters.

We describe two adult patients with the rare syndrome of creatine deficiency due to lack of guanidinoacetate methyltransferase (GAMT). Magnetic resonance imaging (MRI) and MR spectroscopy (MRS) were used to make the diagnosis in two sisters with psycho-motor retardation.

MRI revealed no remarkable structural abnormalities of the brain, with only minor atrophy of the cerebellum and slight hypo-myelination in parietal and occipital regions. However, proton and phosphorous MRS demonstrated an almost complete absence of creatine and phospho-creatine in the brains of both patients. Additionally, abnormally high concentrations of guanidinoacetate and guanidino-acetyl-phosphate were measured in proton and phosphorus spectra, respectively. A lack of creatine and phosphocreatine and low concentrations of creatinine were measured in blood and urine samples, which is pathognomonic of guanidinoacetate methyltransferase deficiency.

Our patients suffer from intractable epilepsy and show a very severe global developmental delay. EEG monitoring led to the diagnosis of “eyelid myoclonia with absences”. Sleep recordings revealed severely disturbed sleep stages with frequent hyper-synchronous activity and seizures.

To our knowledge, we report on the first familial instance of guanidinoacetate methyltransferase deficiency. In addition, the syndrome “eyelid myoclonia with absences” has never been described previously in patients with a metabolic disorder.

Methods

• MR: 2T scanner , 1H-MRS, 31P-MRS
• Subjects: two adult patients with the rare syndrome of guanidinoace-tate methyltransferase deficiency.

White matter proton spectra of a healthy adult (a), patient SB (b) and patient MB (d) as well as gray matter proton spectrum of patient SB (c). All patient spectra demonstrate absence of total Cr and presence of GAA in the brain

Collaborations

Dr. Ritva Sälke-Kellermann, Swiss Epilepsy Clinic, Zurich, Switzerland

Contact

Prof. Dr. Ernst Martin
ernst.martinkispi.uzh.ch

Former Collaborators

Dr. Thomas Loenneker