Reviews in the Neurosciences, 20, 177-180 (2009) © Freund & Pettman, U.K. Brain Anatomy, Cerebral Blood Flow, and Connectivity in the Transition from PVS To MCS Calixto Machado1, Rafael Rodriguez2, Maylen Carballo2, Julius Korein3, Carlos Sanchez-Catasus2, Jesus Perez4 and Gerry Leisman5 'institute of Neurology and Neurosurgery, Havana, Cuba, International Center of Neurological Restoration, Havana, Cuba, 3 Department of Neurology, New York University Medical Center, New York, USA, 4 Hermanos Ameijeras Hospital, Havana, Cuba and 5 F.R. Carrick Institute for Clinical Ergonomics, Rehabilitation, and Applied Neuroscience of Leeds Metropolitan University, Leeds, UK and University of Haifa, Mt. Carmel, Haifa, Israel 2 SYNOPSIS Background: We report a 15 year-old girl with sickle cell disease, who developed important cognitive impairment due to multiple strokes, and who had been diagnosed with PVS. Nonetheless, when she was later admitted to our Institute, according to the presence of inconsistent but clearly demonstrable behavioral evidence of consciousness awareness, we changed our diagnosis to MCS. Methods: This patient was studied by Tl MRI images, co-registration of fractional anisotropy (FA), and SPECT with MRI. Results: Brain structures were mainly preserved in posterior areas of both cerebral hemispheres, although small tissue islands were present in both frontal lobes, mainly preserved in the right one. SPECT showed CBF preservation in posterior brain regions and in the cerebellum, and in those frontal small islands of tissue lateralized to the right frontal lobe; meanwhile FA showed preservation of anatomical connectivity among posterior and frontal brain regions. These remaining cortical regions are also connected with the thalami. Conclusion: These results showing connectivity among posterior and frontal cortical and probably with other subcortical regions, and CBF preservation in these areas, might explain the recovery of minimum awareness despite huge anatomical brain lesions. KEY WORDS persistent vegetative state, minimally conscious state, consciousness, awareness, SPECT, fractional anisotropy, magnetic resonance imaging INTRODUCTION Stroke is one of the most devastating complications of sickle cell disease (SCD) and recurrent strokes may lead to severe cognitive impairment /24,25/. Moreover, the diagnosis of persistent vegetative state (PVS) has become more difficult due to recognition of the minimally conscious state (MCS) /2,3,9,14,18,20,21/. We encountered MCS in a patient with bilateral and severe atrophy of lateral and frontal regions of both hemispheres. She passed through a stage of PVS to MCS. We have considered a possible pathophysiological mechanism to explain her recovery. PATIENT REPORT Address for correspondence: Dr. Calixto Machado, M.D., Ph.D. Institute of Neurology and Neurosurgery Apartado Postal 4268 Ciudad de La Habana 10400, Cuba e-mail: braind@infomed.sld.cu SCD was diagnosed in a girl at age six months. During her first seven years of life she suffered several SCD crises (strokes, symptomatic aplastic anemia, pain, etc.). 177 VOLUME 20, NOS. 3-4, 2009 Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/2/15 2:25 AM 178 C. MACHADO ET AL. Fig. 1: Tl MRI images, co-registration of SPECT and fractional anisotropy with MRI. MRI-T1 images in axial views (first line), reveal marked atrophy consistent with progressive cerebral cell loss in the parietal, temporal and frontal lobes of both hemispheres, associated with dilated ventricles and wide cerebral sulci. Brain structures are mainly preserved in the posterior areas of both cerebral hemispheres. Small tissue islands are present in both frontal lobes, mainly preserved in the right one. Co-registration of SPECT and MRI (middle line) shows maintenance of CBF in the posterior brain regions and cerebellum and in those frontal tissue islands, primarily in the right frontal lobe. Co-registration of fractional anisotropy (FA) and MRI (bottom line) demonstrates relative preservation of anatomical connectivity within the posterior brain regions which are also connected with the frontal tissue islands. These remaining cortical regions are also connected with the thalami. In December 2000, she had a severe headache, and 4 days later her speech was incoherent. A few hours later she became comatose. CT revealed an infarct comprising medial and frontal regions of the right cerebral hemisphere. In the next day she partially recovered consciousness, but 2 days later she again became comatose. Three weeks later she began to show spontaneous eye opening, and a spastic quadriparesis was evident. There was no evidence of gestural or verbal communication, no ability to follow commands, and no visual pursuit or purposeful motor behavior. She was diagnosed as being in a PVS. In December 2002, her parents noted some improvement. Motivated by a TV program about PVS, they contacted us in December 2006, and she was admitted to our center in January 2007. She showed spontaneous eye opening, with active visual and auditory startle reflexes. Brainstcm reflexes were normal, and grasp, palmomental, and sucking reflexes were elicited. The spastic quadriparesis persisted. Nonetheless, she fixated and visually tracked family members as well as a moving mirror, and her eyes oriented toward new sounds. When her father talked to her, she smiled appropriately to the emotional content. She repeated vocalizations with intelligible words and/or gestures in direct response to her father's conversation. She sometimes showed gestural yes/no responses. Accordingly with the presence of inconsistent, but clearly demonstrable behavioral evidence of consciousness awareness, we changed the diagnosis from PVS to MCS. She was studied by Tl MRI with co-registration of fractional anisotropy (FA), and SPECT, as described elsewhere /1,12,13,16,17,19,267. MRI-T1 images in axial views revealed marked atrophy in parietal, temporal and frontal lobes of both hemispheres, associated with dilated ventricles and wide cerebral sulci. Brain structures were mainly REVIEWS IN THE NEUROSCIENCES Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/2/15 2:25 AM BLOOD FLOW AND BRAIN CONNECTIVITIES 179 Fig. 2: SPECT and fractional anisotropy with a higher enlargement in axial (A) and sagittal (B) planes allow better visualization of the findings described in Figure 1. preserved in the posterior areas of both cerebral hemispheres. Small tissue islands were seen in both frontal lobes, mainly on the right side. Coregistration of SPECT and MRI showed active cerebral blood flow (CBF) in the posterior brain regions and cerebellum, and in residual frontal small islands of tissue, lateralized to the right frontal lobe. Co-registration of FA and MRI showed preservation of anatomical connectivity among posterior brain regions, which were also connected with the frontal remaining cortex islands. These remaining cortical regions were also connected with the thalami (Figs, land 2). DISCUSSION Several authors have reported the apparent existence of isolated vestiges of functional brain networks in PVS, suggesting a modular nature of functional networks underlying brain function /ll, 13,15,16,20,22,237. Korein described a male adult with severe bilateral posterior infarcts caused by occlusive vascular disease who was diagnosed as being in a PVS. However, clinical re-examination demonstrated responsive visual behavior to stimuli in the left lower quadrant of the visual field when VOLUME 20. NO. 3-4,2009 Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/2/15 2:25 AM 180 C. MACHADO ET AL. accompanied by shouted questions, demonstrating conscious awareness /10/. In the present case some tissue islands remained in the frontal lobes with preserved CBF. Moreover, co-registration of FA and MRI demonstrated relative preservation of anatomical connectivity within the posterior brain regions that were connected with the frontal tissue islands. The content of consciousness or awareness depends on the integration of dispersed, coherent neural activity and emerges from a statistical process. It is not dependent on the discharge of any particular neuron or neurons but it derives from the synchronous significant departure from randomness across spatially distributed neuronal masses /4-8/. Voss et al. proposed that axonal regrowth could trigger a biological mechanism for late recovery in PVS mi. In our patient we correlated results from MRI (anatomy), SPECT (cerebral blood flow) and FA (connectivity by white matter). Connectivity among posterior and frontal cortical regions and the thalami, and CBF preservation in the cortical areas, might explain the recovery of minimum awareness despite huge anatomical brain lesions. The authors declare no conflict of interest. REFERENCES 1. Cuspineda E, Machado C, Galan L, et al. QEEG prognostic value in acute stroke. Clin EEG Neurosci 2007; 38: 155-160. 2. Machado C, Rodriguez R, Carballo M, et al. Results of proton MRS studies in PVS and MCS patients. Can J Neurol Sei 2009; 36: 365-369. 3. Giacino JT, Malone R. The vegetative and minimally conscious States. Handb Clin Neurol 2008; 90: 99-111. 4. John ER. A neurophysiological model of consciousness. Int J Psychophysiol 2002; 67: 451-452. 5. John ER. The neurophysics of consciousness. Brain Res Rev 2002; 39: 1-28. 6. John ER. A field theory of consciousness. 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